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Mohammed-Sadhakathullah, A.H.; Paulo-Mirasol, S.; Torras, J.; Armelin, E. Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine. Encyclopedia. Available online: (accessed on 07 December 2023).
Mohammed-Sadhakathullah AH, Paulo-Mirasol S, Torras J, Armelin E. Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine. Encyclopedia. Available at: Accessed December 07, 2023.
Mohammed-Sadhakathullah, Ahammed H.m., Sofia Paulo-Mirasol, Juan Torras, Elaine Armelin. "Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine" Encyclopedia, (accessed December 07, 2023).
Mohammed-Sadhakathullah, A.H., Paulo-Mirasol, S., Torras, J., & Armelin, E.(2023, July 01). Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine. In Encyclopedia.
Mohammed-Sadhakathullah, Ahammed H.m., et al. "Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine." Encyclopedia. Web. 01 July, 2023.
Functionalization of Bioresorbable Nanomembranes and Nanoparticles in Biomedicine

Bioresorbable nanomembranes (NMs) and nanoparticles (NPs) are powerful polymeric materials playing an important role in biomedicine, as they can effectively reduce infections and inflammatory clinical patient conditions due to their high biocompatibility, ability to physically interact with biomolecules, large surface area, and low toxicity.

bioresorbable polymers nanomembranes nanoparticles biomedical devices biomedical implants drug delivery

1. Introduction

The development of polymer-based biomedical devices has been aided by the discovery of a new class of materials known as bioresorbable polymers. The term “bioresorbable” has become a widely used phrase to describe this class of macromolecules. The following is a scientifically accepted definition for such materials: a material for which the degradation is mediated, at least partially, from a biological system [1]. Systems made of bioresorbable polymers degrade naturally in the human body; the main advantage is that they do not need to be removed, representing a reduction in surgery complications, helping thus to maximize patient comfort and safety. On the other hand, the rejection of absorbable implants is also a risk to be taken into account, as well as the possible toxicity of the degradation products [2] of said biodegradation. Therefore, bioresorbable polymers must present high biocompatibility and non-toxicological effects belonging to either the polymer itself or the degraded products [3][4]. Thus, in vivo biocompatibility assays of any new bioresorbable material is of utmost relevance [5].
Currently, there are numerous types of bioresorbable polymeric materials with different fabrication, functionalization, and application mechanisms that are being introduced in many fields of human life [6]. The most employed biopolymers belong to polysaccharides compounds such as chitin and chitosan and proteins such as collagen and gelatin [7]. Special mention deserves to bacteria-derived polymers such as polyhydroxyalkanoates (PHA), which usually exhibit non-inflammatory or immune responses in vivo [8]. On the other hand, synthetic bioresorbable polymers belong to petrochemical feedstock monomers with controlled and high purity, and, therefore, they are often preferred for the fabrication of grafts, prostheses, and other biomedical tools compared to biopolymers. Included in this category, the most important classes are polyesters (poly(glycolic acid) (PGA) [9], poly(lactic acid) (PLA) [10][11], and poly(ε-caprolactone) (PCL) [12]) and polyethers such as poly(ethylene glycol) (PEG), even if some of them can be obtained or produced by enzymes bio-based [13]. This development continually extends to envelop more areas, and the direction is slowly moving to target suitable bioresorbable soft materials for specific applications such as tissue regeneration [14][15][16], temporary prostheses [17][18][19], drug carriers [20][21][22], biosensing [23], cancer therapy [24], and others.
Among the applications of such a particular class of bioresorbable compounds, nanomembranes (NMs) and nanoparticles (NPs) (and microspheres) are two of the most common forms being explored. Biological NMs are naturally functionalized systems with channel proteins, essentially present in all living organisms. Artificial NMs comprise biomimetic systems that are multi-functionalized to partially or fully mimic the barrier protection and specific transport properties of natural biological membranes. Either NMs or NPs have thicknesses and diameters, respectively, in the nanometric scale. For instance, a variety of biological systems are well-known as natural NPs for their small dimensions such as vesicles, lipoproteins, magnetosomes, viruses, etc. [25]. NMs can be defined as soft or hard structures with the upper thickness limit of 100 nm (theoretically) [26], and about 2–3 nm (<10 nm) of thickness in the case of cell membranes. NPs can be considered as nanospheres if their diameters range from 10–20 nm to 500 nm as maximum dimension (theoretically), whereas microspheres have micro-dimensions of 500–1000 nm in diameter or higher (giant structures) [22][27].
NMs have become incredible consideration in the last decades due to their exceptional characteristics such as high flexibility, stability, robustness, and molecular permeability along with tunable pore size, shape, and densities [28]. This comes about in the wide range of applications within biotechnology and biomedicine as they are utilized as sensors [29][30], biomotors [31], bio-interfaces for cellular frameworks [32][33][34], antimicrobial surfaces [35][36], and drug release devices [37][38][39], as stated before. In addition, the surface of the NMs can be altered using other molecules such as proteins, drugs, and fluorescent probes, which broaden the applicability of these materials for different medical fields such as wound dressing, tissue engineering, and health care monitoring [40].
In this way, several approaches have been detailed within the literature for synthesizing NMs [28][40][41]. Layer-by-layer (LbL) assembly [42], Langmuir–Blodgett transfer (LB) [43], spin-coating [34][41], dip coating [40], electrophoretic deposition, and cross-linking of self-assembled monolayer (SAM) techniques [44] are some examples of techniques employed for film preparation and functionalization.
On the other hand, functional polymeric micro- and nanospheres, which are commonly employed in chemical catalysis and adsorption systems such as drug delivery [45], have completely different methods for their obtaining than that exemplified for NMs. Those systems are characterized to have a large specific surface area, high adsorption capacity, surface reaction ability, and ease of polymerization method application (aqueous, organic, or water/oil media) [46]. In addition, control over particle size, homogenous distribution, and particle isolation are the most important drawbacks that can hinder reproducibility and good yields over the production processes.
For two decades, the most prominent field of NPs applications has been in the pharmacy, as a drug carrier. The utilization of synthetic biodegradable polymers as microspheres in this area, as well as in NMs applications, has exponentially increased. PLA [47], poly(lactic-co-glycolic acid) (PLGA) [48], and PCL [49] are some of the degradable polymers that can be utilized for this purpose. Polyester copolymers or blends, composed of PLA and other degradable segments (PLGA, PCL, PHA), have been widely investigated due to their enhanced biodegradability and tunable mechanical properties [50]. They can be developed and synthesized with a variety of molecular weights and lactide:glycolide ratios for specific purposes, as in the case of PLGA, while maintaining excellent reproducibility and minimal cost [45].
The most widely used and promising methods for forming nano-sized particles can be categorized into four groups, as detailed by Lee et al. [45]: (i) traditional emulsion-based technologies such as single emulsion, double emulsion, and multiple emulsions; (ii) nano-precipitation, fast expansion of supercritical fluid into liquid, salting out, and dialysis are all examples of precipitation-based procedures; (iii)direct compositing processes such as melting, spray drying, supercritical fluid, and in situ generating micro-particles; (iv) new approaches that include microfluidic techniques and template/mold-based techniques, exemplified for PLA polymer [11][45][47][49].

2. Current Chemical and Physical Modifications of Nanomembranes and Nanoparticles to Afford Specific Functions

2.1. Nanomembranes Functionalization

The function of synthetic NMs would essentially be mechanical and defensive, similar to their biological counterparts if there were no extra capabilities. The majority of roles that biological NMs play are made possible by integrated protein structures that guarantee additional functionalities with respect to synthetic NMs. The main difference at this current point of development is that biological structures provide significantly more complex features than artificial ones, but at the cost of having to use a much smaller toolbox in terms of chemical composition, material options, operating temperature and humidity ranges, and functionalities. Artificial structures use far more rudimentary and flawed processes, but there are a lot more functionalization options available, a bigger variety of materials, and a broader spectrum of pure functions. The latter offers a variety of choices and routes not found in nature.
There are two types of functionalization or modification strategies reported in the literature—bulk and surface. For the scope of this entry, the researchers adhere to surface modification techniques. Surface activation or surface modification refers to the application of some external method to a portion of or the entire surface of the nanomembrane to alter the chemical structure of its interfacial components that interact with the environment [51]. The applied alterations may just be found at the nanomembrane’s volume or they may extend throughout the entire surface area. Chemical [52][53][54], photochemical [55][56], enzymatic [57][58][59], and plasma treatment [60][61] are a few possible activation methods. In surface activation, boundary atoms or molecules may be removed or modified, surface bonds may be broken or created, polar groups may be created or destroyed, etc. The properties of the nanomembrane may undergo drastic alterations as a result of this surface activation, maybe changing by many orders of magnitude after the surface functionalization.

2.2. Nanoparticles and Microspheres Functionalization

The most widely used polymers for NPs preparation are chitosan, alginate, gelatin, PLA, PGA, PLGA, poly(alkyl cyanoacrylates) (PACA), and PCL, which are known for both their biocompatibility and resorbability through natural pathways. Polymers NPs have gained interest due to their intrinsic characteristics to be used in drug delivery, biosensors, imaging, and sensing. The advantages of functional polymeric microspheres, which are commonly employed in chemical catalysis and adsorption, include a large specific surface area, high adsorption capacity, surface reaction ability, and ease of surface modification [62][63].
As was mentioned in the previous section, the most well-known methods to fabricate micro/nano-sized particles are (i) nanoprecipitation, (ii) spray drying, (iii) emulsion aqueous/organic (W/O), and (iv) microfluidic technique [64]. As the aim of this entry is to explore in detail the functionalization of NPs, as well as to explore their potential applications in biomedical fields such as diagnostic agent [63], drug delivery [65], therapeutic agent [66], etc., the researchers will not focus on the NPs fabrication. NPs have been functionalized to modify their properties improving their sensitivity and selectivity towards some specific target, as well as to enhance their specificity to work in complex matrixes.
NPs surface modification can be performed during the synthesis or post-treatment process that is performed by integrating various organic and inorganic molecules at the nanoscale level. Such integration can be conducted through the use of covalent and non-covalent bonds (i.e., hydrogen bonds and electrostatic and van der Waals interactions).

3. Promising Applications of Nanomembranes and Nanoparticles in the Biomedical Sector

3.1. Supported Lipid Bilayers/Proteins

Biological membranes, which are only a few nanometers thick, have a flawless molecular order and are made up of two primary components. Lipids have a structural role by generating a self-assembled continuous bilayer that acts as a diffusion barrier, kept together by hydrophobic interactions. Membrane proteins such as transmembrane proteins and peripheral membrane proteins, which are embedded or transiently connected with the lipid bilayer, are important components of cell metabolism such as exchange and biocatalysis processes. They play a role in cell–cell communication, signal transduction, and ion and nutrient transport. Hence, they are a preferred target for biomedical applications. Because of the intricacy of biological membranes and their interactions with intracellular and extracellular networks, direct research is challenging, and in situ investigations of transmembrane proteins are particularly limited [67]. A variety of biomimetic membranes have been created to solve this problem, with the goal of simulating the basic functionalities of a cell membrane and providing platforms for the systematic investigation of various membrane-related activities. Solid-supported membranes [68], polymer-cushioned membranes [69], hybrid bilayer lipid membranes [70], free-standing lipid layer or suspended-lipid bilayers [71], and tethered bilayer lipid membranes [68][72][73] are all examples of these models.
Lipid surface characteristics such as charge and substrate type (hydrophilic/hydrophobic) influence how they self-assemble on the polymeric substrate. Lipid self-assembly occurs on polymer surfaces primarily as a result of electrostatic attraction and hydrophobic interactions. Charged vesicles can be electrostatically attracted to oppositely charged polymeric NPs by incorporating anionic or cationic lipids into a phospholipid bilayer [74]. In order to lower the system’s free energy, neutral phospholipids such as phosphatidylcholine and dipalmitoyl phosphatidylcholine self-assemble onto hydrophobic polymeric surfaces. In accordance with this concept, the surface functionalization of PLGA NPs using lipids has shown promising results in the creation of PLGA-based clinical nanomedicines. Enhancing the target specificity of the carrier through surface engineering with various lipids also boosts its physicochemical characteristics and NP-cell interactions such as cellular membrane permeability, immunological responses, and long circulation half-life in vivo [75].
According to Meyer et al. [76], adaptable bioorthogonal ligation reactions may enable modular protein conjugation to the lipid-coated particle surface. This work developed a way to incorporate biologically relevant proteins on a fluidic synthetic lipid membrane with a predetermined anisotropic shape by combining manufacturing techniques for biodegradable particle creation, thin film stretching, lipid coating, and flexible biomolecular conjugation. This protein presentation can be supported by particles of various shapes and variable radius of curvature, and it replicates the dynamic membrane characteristics of real cells. With the display of laterally movable proteins on the surface of anisotropic biodegradable particles, allowing independent control of the particle’s geometry and permitting the encapsulation of biological cargos, this biotechnology can enable more exact mimicking of natural cells [77].

3.2. Biosensors

The development of biosensors for the detection of either biomarkers or states of movement of the human body using nanostructures, either by means of membrane composites and/or NPs with electrochemical properties, has aroused much interest. The high surface-to-mass ratio of these nanostructures provides larger areas of interaction with the biomolecules to be detected, thus improving the sensitivity of the final device. The use of natural polymers with their high biodegradability and biocompatibility, together with their ability to immobilize enzymes and other conductive materials, makes them often used in the integration of biosensors.
Flexible biosensor in point-of-care healthcare applications for the detection of various proteins and biomarkers is a constantly growing field. An important added value is that offered by Xu et al. [78], who reported a flexible, fully organic, biodegradable, biocompatible impedimetric biosensor to monitor vascular endothelial growth factor (VEGF). For this, a conductive ink consisting of a photoreactive silk sericin coupled with a conductive polymer was fixed by photolithography on a flexible free-standing fibroin substrate. Detection was performed through the antibody against VEGF, which was immobilized within the conductive matrix. The biosensor was shown to be highly sensitive and selective for VEGF, even in challenging biofluids such as human serum. However, the biosensoring membranes are likely free-standing but supported on a skeleton device to facilitate their manipulation depending on their final use. For instance, a novel electrochemical biosensor for the detection of human epidermal growth factor receptor 2 (HER2), a breast cancer biomarker was presented [79]. This was shown to be very feasible for use in complex biological samples and human serum with quite acceptable precision. Here, the antifouling detection interface is based on the conductive polymer PEDOT and a biocompatible peptide hydrogel. The peptide hydrogel was prepared from an engineered short peptide of Phe-Glu-Lys-Phe and functionalized with a fluorene methoxycarbonyl group (Fmoc-FEKF) in order to preserve the activity of the immobilized anti-HER2 antibody molecules and their good hydrophilicity. This facilitated effective alleviation of nonspecific adsorption or biofouling, thus extending its functionality.
On the other hand, the stability and activity of complex proteins used as a biosensor molecule can be greatly compromised by the way it is immobilized within a foreign environment. Thus, new methodologies that try to mimic the natural environment of these proteins are emerging. It has recently been shown that lipid, polymeric, and hybrid planar membranes based on mixtures of lipids and copolymers on a solid support provide a more favorable environment for driving the selective and functional binding of a model redox protein such as cytochrome c (cyt c) [80]. In this case, the authors showed how polymer membranes provide sufficient chemical versatility to support covalent binding with protein (cyt c), while lipid membranes provide the flexibility and biocompatibility that facilitate the insertion of the protein (cyt c) through its hydrophobic part. This example showed how hybrid membranes combine the most promising features of lipids and polymers and enable the binding of cyt c with covalent binding as well as its insertion driven by hydrophobic interactions. Indeed, these results support the development of complex and versatile hybrid bio-interfaces containing both lipid and polymer domains.
Nanoparticle size allows a better diffusion inside biological systems. Customized biofunctionalization methods can transform inert NPs into hybrid nanosystems capable of targeting specific receptors that trigger specific cellular responses dictated by proteins located on their coating layer. Navarro–Palomares et al. [81] were able to mimic the specific cellular entry mechanisms of certain natural ligands. In fact, they were able to reproduce the molecular cues found in Shiga toxin to target the biosensing NPs into head and neck cancer (HNC) cells bearing the globotriaosylceramide receptor (GB3). To achieve functional biomimetics, they coated SiO2 and Fe3O4@SiO2 NPs with a recombinant chimeric protein containing the harmless B-domain of Shiga toxin genetically fused to a nanomaterial-binding sequence. The entry of biosensor NPs into tumor cells allows for better identification and/or subsequent treatment.
Nevertheless, sensor NPs are usually found immobilized within a polymeric matrix to give them mechanical support or to reinforce their biosensor character. Recently, a new biosensor that can potentially be used for the determination of L-asparagine in the diagnosis and treatment of leukemia has been proposed [82]. It is an electrochemical biosensor based on chitosan alginate (CA) NPs that contain L-asparaginase trapped inside. The NPs were deposited on a nylon membrane that covered an ion sensitive electrode (ISE) to detect the ammonium ions (NH4+) emitted in the reaction of L-asparagine with L-asparaginase. Furthermore, a promising strategy in the development of a new generation of multifunctional flexible wearable biosensors can be seen in the work proposed by Wei et al. [83]. Specifically, a combination of strawberry-type BaTiO3 (BT) inorganic particles, soy protein isolate (SPI) chains, polyethylene glycol-200 (PEG-200), and glycerin (GL) to fabricate an SPI-based membrane material (SPI-BT@Ag0.5) was proposed. This material simultaneously exhibits outstanding yield strength (37.6 MPa), toughness (19.0 MJ m−3), and fatigue strength, as well as being low-cost, easy-to-process, and highly conductive. Successful monitoring of human physiological signals and motion states in combination with excellent biocompatibility and biodegradability were reported.

3.3. Selective Drug Delivery

Promising biodegradable and biocompatible delivery systems for medications and other therapeutic agents are being tested in many research projects using biopolymeric nanomaterials of various origins. The experiments sought to increase the loaded cargo’s bioavailability and therapeutic impact while also guarding against any potential negative side effects. Bioactive substances such as polyphenols, conventional medications such as those used to treat cancer, antibiotics, natural extracts, and essential oils are just a few examples of the various sorts of cargo being loaded [84]. They are chemically unstable as a result of their susceptibility to external factors such as light, heat, and oxygen. Moreover, they are rapidly metabolized and have limited water solubility. By integrating bioactive substances into nanocarriers such as biopolymeric nanomaterials, these restrictions can be effectively addressed. They can also lower the dosage of bioactive substances needed, lowering the risk of additional negative effects [85]. Here, the emphasis is on the most up-to-date toolkit of literature.
Combinational therapeutic strategies using chitosan (CS), ampicillin (AMP), and pegylated-ZnO (P-ZnO) NPs were developed to increase antibacterial efficacy against infections that produce extended-spectrum beta-lactamases (ESBLs) and are antibiotic-resistant [86]. To ensure the efficacy of the biological qualities, AMP was first loaded onto the fully manufactured CS NPs using adsorption methods in this research. This was followed by a coating with P-ZnO NPs. It was discovered that CS-AMP-P-ZnO NPs had greater antibacterial activity than CS-AMP and AMP alone. Additionally, it was shown using cell membrane potential, protein leakage, and biofilm inhibition assays that the combinational treatment strategies greatly increased the antibacterial and biofilm inhibition efficacy by changing the permeability of the cell membrane. This research implies that the developed combinational antibacterial medication may be a possible treatment for several bacterial illnesses.
Nanoparticles have long been the focus of attention in the biomaterial world as a medicine delivery mechanism. A new paradigm of biomaterials with a wide range of applications based on prolonged drug release is made possible by the incorporation of NPs into other biodegradable platforms such as patches, implants, and films. Lin et al. [87] described the delivery of non-steroidal anti-inflammatory drugs (NSAIDs) by degradable biopolymer microneedle patch for the treatment of rheumatoid arthritis. The neutrophil membrane (NeuM) was used to coat the polymeric NPs that contained the NSAIDs in this dual drug delivery patch before they were inserted into the microneedle patch for local transdermal delivery. The microneedle patch progressively dissolves and releases the encapsulated NPs when used on murine models. The surface modification of PLGA NPs by NeuM is anticipated to mimic the source cell neutrophil, boosting the inflammatory joint targeting and cytokine adsorption of the NPs. The hyaluronic acid microneedle is intended to improve the transdermal absorption of indomethacin. This work offers a potential combination approach to treating rheumatoid arthritis clinically, which may potentially widen the approach to treating autoimmune disorders with anti-inflammatory drugs.
Additionally gaining popularity as a potential drug release platform are polymeric thin films. Prodigiosin (PG), a bacterial pigment with potent anticancer properties, was coupled with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to create functionally improved PHBV-based biomaterials [88]. The acquired samples were made using a straightforward solvent casting technique, and had a film thickness ranging from 115.6 to 118.8 µm. Moreover, the films were cytotoxic to colon cancer cells, demonstrating the potential for the PHBV/PG biomaterials to be employed in anticancer therapy.

3.4. Wound Dressing and Skin Regeneration

To promote wound healing, the primary purpose of wound dressings is to provide a moist, hospitable environment. The following characteristics are necessary for a dressing to be effective: Wound dressings should (i) be compatible with living tissue, (ii) non-toxic, (iii) compliant with tissue, (iv) permeable to water vapor, (v) able to absorb water, (vi) have sufficient mechanical characteristics, and (vii) shield the wound from contamination [89][90]. Researchers in biomedical engineering have recently focused heavily on biodegradable-based dressings made up of natural and synthetic materials for effective and speedy management of wound damage along with lowering the bacterial infection rate. This biopolymeric-based technology has the ability to overcome all the drawbacks of auto- and allografting, and is thought to have a fantastic approach to the process of skin repair and regeneration [91].
Film, foam, gel, and hydrocolloid are just a few of the modern forms that wound dressings can take. The films’ flexibility allows them to conform to the shape of the patient’s body, even in tight spaces such as around the joints, allowing the medication to be applied directly to the wound. The films are gas permeable and prevent bacteria from entering the wound site [92][93]. In light of this, a gellan gum (GG)-based hydrogel film (Ag@TiO2NRs/GG) containing Ag-loaded TiO2 nanorods (TiO2 NRs) was recently published [94]. TiO2NRs, which have an elongated structure and are considered cutting-edge one-dimensional fillers, were utilized in the manufacturing process of hydrogel film. As a secondary form of reinforcement, the Ag particles are incorporated into the hydrogel film in an effort to improve its properties. The presence of Ag in conjunction with TiO2NRs fosters both the viability and proliferation of cells. By the fourteenth day after receiving treatment with Ag@TiO2NRs/GG hydrogel film, wounds on rats had totally healed. An ultrasound scan of the treated skin reveals an increase in the thickness of all three layers of the epidermis, the dermis, and the subcutis, which is evidence of successful regeneration of the skin’s tissue. Because hydrogels are the most commonly used materials for 4D bioprinting in tissue engineering, the authors decided to employ them for the purpose of achieving on-demand features such as controlled movement, programmable shape alterations, on-demand conveyance, or deterioration.
The utilization of herbal biogenic materials is one inventive method for treating wound infections because of the minimal toxicity and side effects linked with them. Recent years have seen a proliferation of publications in the literature that take this approach. Honey’s naturally occurring antibacterial properties are put to good use in a novel wound dressing material that is composed of gellan gum (GG) and guar gum (GGu) biopolymeric film [95]. The films were made using the solvent casting method, demonstrating the impact of increasing the honey concentration in the system. Enhanced honey concentration in the polymer matrix reduced the swelling capacity of the wound dressing films and enhanced the degradation of the films. Films with a low water vapor transmission rate (WVTR) were appropriate for use as bandages on wounds, while an increase in honey concentration resulted in a higher WVTR. The GG/GGu-H-2.5 film shows promise as a material for efficient wound dressing applications based on evaluations of its mechanical strength, antioxidant characteristics, and wound healing qualities. This novel wound dressing material is an interesting addition to the toolbox.

3.5. Actively Targeted Chemotherapeutics

Chemotherapy enhancement has seen widespread use of biodegradable nanoplatforms to avoid the extensive use of chemotherapeutic chemicals that cause damage to healthy tissues. Furthermore, its prolonged use results in systemic toxicity and unfavorable consequences that significantly reduce the maximum tolerable dose of anticancer drugs, and hence reduce their therapeutic efficacy. Most solutions focus on creating highly efficient drug delivery systems that precisely deliver drugs to tumor locations, improving chemotherapy effectiveness while reducing damage to normal cells. Specific drug delivery is based on endogenous or external stimuli such as temperature, light, pH, acidic and reductive conditions, etc. [96][97].
Many nanostructures such as vesicular, dendritic, hydrogel, polymeric, and composite NPs have been developed as drug delivery systems to encapsulated agents (e.g., chemotherapeutic drugs) and their delivery to specific targets. To minimize the risk factors, the research groups are focused on working with resorbable polymers, which can be reabsorbed into the body after the treatment without any harmful products [98]. Polymeric NPs present the optimal properties to be used as a chemotherapeutic platform since they can regulate and transport the drug to cells avoiding the damage of other healthful cells.

3.6. Imaging and Diagnostics

Bioimaging is a very powerful and interesting technique that has been developed thanks to its ability to monitor biological processes, which means that diseases can be detected and controlled in vivo. Several methods have been created and developed to obtain accurate images of tumors, cells, bacteria, etc. Among them, the most widely used methods are magnetic resonance imaging (MRI), computed tomography (CT), ultrasound imaging, and positron emission tomography (PET). In the deployment of these methodologies, polymeric platforms have been used because, compared to other materials, they present some important advantages to highlight such as photostability, biocompatibility. and bioresorption.
For instance, Geng et al. [99] synthesized polymer NPs using poly (DL-lactide-co-glycolide) as an encapsulation matrix and PVA as an emulsifier. The fluorogen 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)-phenyl)amino)-phenyl)-fumaronitrile(TPETPAFN) was encapsulated on that matrix. A co-encapsulation matrix based on poly([lactide-co-glycolide]-b-folate [ethylene glycol]) (PLGA-PEG-folate). NPs surfaces were functionalized with folic groups, which were applied for targeted cellular imaging.
Another well-known technique used in bioimaging is fluorescence microscopy, featuring highly efficient light collection, multiple emissive wavelengths, ease of modification, photostability, and low cytotoxicity. In 2021, Ueya and coworkers [100] encapsulated a red dye (IR-1061) in polymeric micellar NPs formed from poly(ethylene glycol)-b-poly(lactide-co-glycolide). It is interesting to note that PEG-b-PLGA forms a stable polymeric micellar nanoparticle in an aqueous environment (denoted as OTN-PNP). A facile synthesis based on nanoprecipitation was performed and the photostability was enhanced by adding an organic fluorophore, di(thiophene-2-yl)-diketopyrrolopyrrole (DPP) encapsulated within OTN-PNPs. The influence of the molecular weight of the copolymers on the stability of the polymer micellar NPs in aqueous media and the emission intensity of IR-1061 in the polymer NP were studied. In this study, it was concluded that OTN-PNPs with a higher molecular weight of PLGA cores showed higher emission and stability under physiological conditions.
Theranostic nanomedicine is recently emerging as a novel treatment that combines therapeutic and imaging functionalities in a single platform. In recent years, many research efforts have been invested in achieving this objective. The resulting nanosystems, capable of diagnostics, drug delivery, and therapeutic response monitoring, are expected to play an important role in the emerging field of customized medicine [101]. The fact that many nanoplatforms are already imaging agents makes it easy to build these new agents with additional built-in functionality. Its surface chemistry allows it to easily incorporate pharmaceuticals and advertise them as theranostic nanosystems. Nanoparticle-based theranostics, a descendant of the two aforementioned approaches, is still in the early stages of development. Nanoparticle-based imaging and therapy are struggling to make it to clinical trials. However, nanoparticle-based theranostics has already gained interest due to the impetus provided by advances in nanotechnology and the need for more individualized therapy. Some research groups have already been working on different NPs such as silicon NPs, quantum dots (QDs), or gold NPs [102]. In addition, various types of biodegradable polymeric theranostic nanoplatforms are being developed such as fluorescence imaging, polymer-based super-paramagnetic NPs, iron oxide NPs, ultrasound-triggered polymeric NPs, and polymer NPs bearing radionuclides [103]


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