Polymeric Nanoparticles for Drug Delivery

Abstract

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.

Figure 1

The principal biological environments and barriers polymeric nanoparticles must overcome in order to achieve efficient therapeutic delivery.

Figure 2

A corona is generated around the nanoparticle surface via the attachment of a variety of proteins to its surface. This protein corona affects how rapidly particles are cleared by the immune system, and is highly dependent on particle size, shape, and charge.

Figure 3

A selection of the physicochemical properties of polymeric nanoparticles that can impact circulation time. They encompass size, shape, and surface chemistry, including surface charge and the incorporation of targeting moieties.

Figure 4

A schematic representation of a biofilm and the properties that affect bacteria targeting. These properties include pH and oxygen gradients throughout the film, as well as the protective extracellular polymeric substances (EPS) matrix and intrafilm water channels.

Figure 5

A schematic representation of the tumor microenvironment, and two different mechanisms, passive and active targeting, by which nanoparticles deliver drugs to tumors. Passive tumor targeting is achieved through the EPR effect, which results from the increased permeability of tumor vasculature and ineffective lymphatic drainage. Active tumor targeting is achieved by functionalizing nanoparticles with targeting ligands that can bind to specific cellular receptors present in the tumor mass. Reproduced with permission from ref. (56). Copyright 2019, American Chemical Society.

Figure 6

Schematic illustrations of proposed endosomal escape mechanisms including: membrane fusion—nanoparticle materials, usually lipids or amphiphilic materials, fuse with the endosomal membrane, releasing the cargo to the cytosol; osmotic rupture due to the proton sponge effect—polymeric materials that are capable of buffering the acidity of the endosome increases the influx of chloride counterion ions and lyses the endosome due to higher osmotic pressure; particle swelling—nanoparticle swelling ruptures the endosomal membrane due to increased mechanical strain; and finally membrane destabilization—free polymers resulting from the disassembly of pH-responsive nanoparticles can interact with endosomal membrane, prompting membrane destabilization and cargo release to the cytosol. Reproduced with permission from ref. (73). Copyright 2019, American Chemical Society.

Figure 7

(A) The endosomal escape of pH-responsive polymeric nanoparticles was quantified with the SLEEQ assay. (B) Comparison of endosomal escape efficiencies in different systems obtained by SLEEQ assay. Reproduced with permission from ref. (7, 81). Copyright 2021, American Chemical Society (A) and Copyright 2017, Wiley-VCH (B).

Figure 8

A selection of preeminent poly(amino acids) used in drug delivery; poly(l-glutamic acid) (PGlu), poly(l-aspartic acid) (PAsp), poly(l-lysine) (PLL), and poly(l-arginine) (PArg).

Figure 9

General chemical structures of polysaccharides used in drug delivery: chitosan, hyaluronic acid (HA), and dextran.

Figure 10

General chemical structures of common glycopolymers used in drug delivery: mannose, galactose, glucose, and fructose functionalized methacrylates: poly(2-(β-d-mannopyranosyloxy)ethyl methacrylate), poly(2-(β-d-galactopyranosyloxy)ethyl methacrylate), poly(6-O-acryloyl-β-d-glucoside, and poly(1-O-acryloyl-β-d-fructopyranose), respectively.

Figure 11

Common examples of polyesters used in drug delivery: poly(glycolic acid) (PGA), poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLA), and poly(ε-caprolactone) (PCL).

Figure 12

General chemical structures of phosphate-based polymers: polyphosphoesters (PPEs) and poly(phosphonates) (PPNs).

Figure 13

General classes of vinyl polymers used in drug delivery; acrylates, methacrylates, acrylamides and methacrylamides with common examples: poly(hydroxyethyl acrylate) (PHEA), poly(methyl methacrylate) (PMMA), poly(N,N-dimethylacrylamide) (PDMA), poly(N-(2-hydroxypropyl) methacrylamide (PHPMA), poly(vinyl alcohol) (PVA), and polystyrene (PS).

Figure 14

Common examples of cyclic ketene acetals (CKAs) and their general polymeric ester products after radical ring-opening polymerization: 2-methylene-1,3-dioxepane (MDO), 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), 2-methylene-4-phenyl-1,3-dioxolane (MPDL), and 2-methylene-1,3,6-trioxocane (MTC).

Figure 15

General chemical structures of poly(ethyleneimine) (PEI): linear PEI and branched PEI.

Figure 16

General chemical structures of polymer building blocks that are used as hydrophilic components for nanoparticle delivery systems. (A) PEG and hydrophilic PEG alternative polymers: mPEG, POEGMA, PG, POx, PHPMA, PDMA, PAAm, PNAM, and polysarcosine (PSar). (B) Zwitterionic polymers: poly(carboxybetaine acrylamide) (PCBAA), poly(carboxybetaine methacrylate) (PCBMA), poly(sulfobetaine methacrylate) (PSBMA), and poly(methacryloyloxyethyl phosphorylcholine) (PMPC).

Figure 17

Nanoparticles comprising highly functionalized polymers can respond to a myriad of stimuli to enhance drug-delivery performance. These stimuli include, but are not limited to, temperature, light, redox and enzymatic environment, pH, and exposure to a magnetic field.

Figure 18

A selection of pH-responsive polymers and their charge transitions; (A) polymers with weakly basic amino groups: PDEAEMA, PDMAEMA, PDPAEMA, and P4VP. (B) Polymers with weakly acidic carboxylic groups: PMAA, PPAA, poly(acrylic acid), and PVBA.

Figure 19

General examples of pH-responsive linkages and their corresponding hydrolyzed products. Adapted with permission from ref. (241). Copyright 2019, Wiley-VCH.

Figure 20

Common examples of redox-responsive linkers and their degradable products.

Figure 21

Common examples of enzyme-responsive linkages used in the design of enzyme-responsive polymers for drug delivery.

Figure 22

Common examples of light-responsive functional groups used in the design of photo-responsive polymers.

Figure 23

General examples of self-immolative polymers and their depolymerization mechanisms: (A) QM-based SIPs, with only 1,6-elimination, (B) PEtG/PGAMs, and (C) poly(disulfides).

Figure 24

The packing parameter, p, is a concept that predicts the morphology of nanoparticles based on amphiphilic block copolymers. The various different morphologies of nanoparticles for different ranges of p are shown above, where p is proportional to the volume of the hydrophobic component, v, and inversely proportional to its length, l, and the cross-sectional area of the hydrophilic component, a.

Figure 25

A schematic illustration of nanoprecipitation. Polymers are dissolved in a miscible solvent, which is then added to water. The polymers, which are insoluble in an aqueous environment, self-assemble into nanoparticles as the solvent dissolves into the water.

Figure 26

A schematic illustration of the solvent evaporation technique. Polymers are dissolved in a miscible solvent that is then emulsified in water. As the solvent evaporates, the polymers self-assemble into nanoparticles.

Figure 27

A schematic illustration of emulsion polymerization. The monomer is added in the form of a droplet to a solution containing surfactant micelles. As monomers migrate from the droplets to the micelles, polymerization occurs in the micelles, forming larger polymeric nanoparticles.

Figure 28

A schematic illustration of polymerization-induced self-assembly (PISA). Two processes, polymerization and self-assembly, are combined into one step. As the monomers polymerize, they self-assemble at the same time, forming a suspension of nanoparticles.

Figure 29

A schematic illustration of spray drying. A fluid containing nanoparticles is atomized into droplets. When these droplets are passed through heat, the rapid evaporation of the solvent forms nanoparticles, which are then separated and collected.

Figure 30

A schematic illustration of layer-by-layer assembly, a form of templated assembly. A core is gradually coated with separate polymeric layers to form a nanoparticle. Other building blocks can also be included such as inorganic nanoaprticles or drugs. In this example, oppositely charged polyelectrolytes form a layered nanoparticle through electrostatic attraction.

Figure 31

Nanoparticles can encapsulate a range of diverse therapeutic cargo, from small-molecule drugs to large biomacromolecules such as proteins and nucleic acids. These therapeutics can be loaded through physical interactions such as the hydrophobic effect, electrostatic interactions, as well as covalent conjugation.

Figure 32

Drug–polymer conjugates can be created via an enormous amount of distinct chemical linkages. A selection of the principal linkages are depicted, including stimuli-responsive and hydrolyzable moieties as well as common conjugate forming reactions.

Figure 33

Two types of SILs and their fragmentation mechanism: (A) elimination and (B) cyclization.

Figure 34

Drug integration as the polymer backbone (therapeutic moieties are highlighted in red). Panels A–D represent specific studies using these degradable backbones that are referenced in the text.

Figure 35

A myriad of different spherical nanoparticle designs. The hydrophobic sections are shown in red, and the hydrophilic sections are shown in blue. (A) Core–shell nanoparticle, (B) polyion complex, (C) polymersome, (D) nanogel, (E) star polymer, and (F) hyperbranched polymer.

Figure 36

A schematic illustration depicting the self-assembly of micelles.

Figure 37

(A) A redox-responsive micelle based on the self-assembly of a PEG-b-PLGA amphiphilic block copolymer. This micelle was functionalized with the disulfide bond, which is reducible under endogenous conditions, allowing for superior therapeutic cargo delivery, as well as enhanced cellular uptake in a lung cancer model. (B) A temperature-responsive PEG-b-PNIPAm micelle cross-linked via supramolecular hydrogen bonding. This micelle was able to undergo reversible temperature-induced swelling and shrinking, not only due to the presence of PNIPAm, but also due to the quadruple hydrogen bonding cross-linking imbued by the UPy unit. Adapted with permission from ref. (442, 443). Copyright 2018, Elsevier (A) and Copyright 2017, Royal Society of Chemistry (B).

Figure 38

A schematic illustration depicting the self-assembly of distinct core–shell polymeric nanoparticles.

Figure 39

Two sophisticated core–shell polymeric nanoparticle designs. (A) Emulsion polymerization, a more clinically relevant preparation procedure, was employed to synthesize pH-responsive nanoparticles. These nanoparticles were based on the charge shifting polymers PDPAEMA and PDEAEMA, and underwent swelling in response to acidic conditions that mirrored the endosomal environment. (B) A curcumin-loaded nanoparticle based on a PEG shell and a PCL core. This nanoparticle incorporated both a cell penetrating peptide and a tumor targeting peptide, and showed strong tumor penetration and anti-tumor efficacy. Adapted with permission from ref. (83, 460). Copyright 2022, Wiley-VCH (A) and Copyright 2020, Springer Nature (B).

Figure 40

A schematic illustration depicting the self-assembly of polyion complexes.

Figure 41

A PIC was designed that was able to edit various cell genomes through the delivery of two sets of RNA, Cas9 mRNA, and single guide RNA (sgRNA). The ∼65 nm PIC was formed via the assembly of a cationic block copolymer composed of PEG and modified PAsp, and anionic RNA. This design successfully loaded, protected, and delivered RNA to neurons when injected into mice, yielding cerebral gene editing. SgRNA is a single strand of RNA that forms complexes with ceratin enzymes to target and often cleave sections of DNA. Adapted with permission from ref. (468). Copyright 2021, Elsevier.

Figure 42

A schematic illustration depicting the self-assembly of polymersomes.

Figure 43

(A) A dual functional PEGylated polymersome that utilizes the redox-responsive disulfide moiety, and a pH-responsive charge shifting monomer DEAEMA, for sensitive nucleotide delivery. (B) A PEGylated PCL-based polymersome design that incorporates peptide–polymer conjugation for tumor targeting, and stimuli-responsive morphological change for enhanced drug delivery. Reproduced with permission from ref. (483, 488). Copyright 2019, Nature (A) and Copyright 2021, Wiley-VCH (B).

Figure 44

A schematic illustration depicting the self-assembly of nanogels.

Figure 45

Drug–polymer conjugation was used to design a nanogel that was able to efficiently encapsulate PTX (TAX), a hydrophobic drug. Specifically, PTX was conjugated to poly(acrylic acid), a mucoadhesive polymer, which formed a nanogel when cross-linked with cyclodextrin. The enhanced targeting performance and high loading efficiency of this nanogel yielded strong anti-tumor performance. Reproduced with permission from ref. (503). Copyright 2019, Wiley-VCH.

Figure 46

A light-responsive hyperbranched polymer that is able to encapsulate and deliver the insoluble chemotherapeutic drug DOX. This hyperbranched polymer was composed of UV degradable nitrobenzyl groups and stabilized by a DNA–polymer conjugate (aptamer). Cleavage at 365 nm irradiation resulted in controlled drug release and anti-tumor efficacy. Reproduced with permission from ref. (531). Copyright 2018, Wiley-VCH.

Figure 47

Hybrid nanoparticles are polymeric nanoparticles that incorporate a fraction of inorganic material for a variety of therapeutic purposes. Depicted are four of the most common inorganic materials that have been incorporated within polymeric nanoparticles: gold nanoparticles, silica, iron oxides, and quantum dots.

Figure 48

(A) A Schematic illustration of the self-assembly of QDs and amphiphilic copolymers into two distinct nanoparticle assemblies of magneto-core/shell assemblies (left) and magneto-micelles (right). (B) A TEM image of a magneto-core/shell assembly prepared with 2.8 nm iron oxide particles using DMF as the common solvent. (C) A TEM image of a magneto-micelle prepared with 2.8 nm iron oxide particles using THF as the common solvent. Reproduced with permission from ref. (551). Copyright 2013, American Chemical Society.

Figure 49

A Schematic representation of the formation of RGD-functionalized Au NPs-loaded hybrid polymersome via a double emulsion process (w/o/w). Reproduced with permission from ref. (583). Copyright 2016, Royal Society of Chemistry.

Figure 50

A selection of non-spherical polymeric nanoparticle designs consisting of (A) rod-like architecture, (B) worm-like architecture, and (C) disk-like architecture.

Figure 51

(A) A Schematic diagram of the PRINT process compared to traditional imprint lithography. (B) Different types of morphologies that are obtained by PRINT: (i) trapezoidal PEG particles, (ii) bar PEG particles, (iii) conical PEG particles, (iv) arrow PEG particles. In PRINT, the use of a non-wetting substrate allows for the generation of isolated particles. Reproduced with permission from ref. (609). Copyright 2005, American Chemical Society.

Figure 52

SEM images of nanoparticles with different shapes: A) spheres, B) rods, and C) discs. These non-spherical nanoparticles were prepared from polystyrene spherical particles using the mechanical deformation process discussed in Section 6.1.2. Reproduced with permission from ref. (616). Copyright 2016, Elsevier.

Figure 53

A schematic illustrating the self-assembly of PEG-Dlinkm-R9-PCL into PEG detachable polymeric micelleplexes for siRNA delivery. (i) Self-assembly of PEG-Dlinkm-R9-PCL into nanoparticles in aqueous solution and binding with siRNA to form micelleplexes (D_m-NP_siRNA). (ii) Systematic administration of D_m-NP_siRNA. (iii) Prolonged circulation of micelleplexes with the protection of stable PEG layer until reaching the targeted tumor site. (iv) Recognition of D_m-NP_siRNA by tumor cells and Dlink_m undergoes degradation when exposed to low pH of extracellular environment to increase the cellular uptake. Reproduced with permission from ref. (695). Copyright 2015, American Chemical Society.

Figure 54

A schematic representation for the synthesis of HA-PPEGMA-b-P(MMA-co-Cy5MA) block copolymer (1–4), formation of curcumin-loaded HA-modified micelles via self-assembly (5), formation of multi-component drug-delivery system encapsulating curcumin-loaded HA-modified micelles into an alginate microcapsule (6), oral delivery for the site-specific drug release at tumor cells (7, 8). Reproduced with permission from ref. (747, 749). Copyright 2020, Wiley-VCH.

Figure 55

(A) Schematic representation of self-assembly of tri-block copolymer (PDDT) composed of PEG, pH-sensitive copolymer (P(DPAEMA₅₀-co-DMAEMA₅₆)), and positively charged poly(N,N,N-trimethylammonium ethyl methacrylate) (PT, also known as PTDMAEMA) forming pH-responsive polymeric polyplexes (PDDT-Ms/siRNA) for siRNA delivery. (B) After cellular uptake, PDDT-Ms/siRNA polyplexes undergo pH-induced disassembly within the acidic pH of endosome resulting in cytosolic release of siRNA to block the cancer cell proliferation. Reproduced with permission from ref. (764). Copyright 2021, American Chemical Society.

Figure 56

A schematic representation of the chemical structures of amphiphilic cationic prodrug SA-MTO and pH-responsive polymer MeO-PEG-b-PPMEMA (A), formation of pH-responsive polymer–prodrug hybrid nanoparticle for combinational cancer therapy using siRNA and MTO delivery (B), Western blot (C, D) analysis of PLK1 expression in the tumor tissues of the MDA-MB-231 xenograft tumor bearing nude mice treated with siLuc NP15 (control NPs) or siPLK1 NP15 (siPLK1-loaded nanoparticle). Tumor size (E) and tumor weight (F) of the MDA-MB-231 xenograft tumor-bearing nude mice treated with PBS, naked siPLK1, free MTO, and siLuc NP15 (control NPs), and siPLK1 NP15. Reproduced with permission from ref. (765). Copyright 2019, American Chemical Society.

Figure 57

(A) A schematic representation for the preparation of GOD and DiABZI co-loaded polymersome nanoreactor (D/G@PFc) via self-assembly of block copolymer, poly(ethylene glycol)-b-poly(2-(methacryloyloxy) ethyl ferrocene-carboxylate-co-2-(piperidin-1-yl)ethyl methacrylate) (PEG-b-P(FcMA-co-PEMA)) in an aqueous solution at pH 7.4. (B) The cascade reactions pathway to enhance anti-tumor immunity via combination of chemodynamic-immunotherapy. Reproduced with permission from ref. (770). Copyright 2021, Wiley-VCH.

Figure 58

A schematic illustration of the antigen processing and presentation pathway in a dendritic cell leading to the activation of CD4⁺ T cells (left), and CD8⁺ T cells (right). CD4⁺ T cells can be differentiated into Th1, Th2, Th17, and Tfh cells, which release various cytokines such as interferon-γ (IFN-γ) and interleukins (IL-2, IL-4, IL-5, IL-17, and IL-21), to stimulate both humoral and cellular immune response, and activation of CD8⁺ T cells leads to the killing of mutated or infected cells. Reproduced with permission from ref. (778). Copyright 2021, Elsevier.

Figure 59

A) Schematic representation of mannosylated polymer nanoparticles (P-I/II micelles) for the delivery of both MHC-I and MHC-II epitopes to DCs. B) Percentage of IFN-γ⁺ and TNF-α⁺ CD8⁺ T cells in the spleen after restimulation with SIINFEKL peptide; P-I/II micelles induced a significant increase in the number of IFN-γ- and TNF-α-producing CD8+ T cells in the splenocytes when stimulated with SIINFEKL compared to phosphate buffer saline (PBS) control and free peptide. C) Tumor growth inhibition curve of B16F10 tumor-bearing mice treated with PBS, free peptides, control mannosylated polymer without antigen conjugation (MAN-P), and P-I/II micelles. Reproduced with permission from ref. (819). Copyright 2022, Wiley-VCH.

Figure 60

A stimuli-responsive, bacteria targeting dual functional nanoparticle for the delivery of rifampicin against S. aureus. Targeted delivery was achieved via the incorporation of mannose receptors for macrophage internalization, and the pH triggered exposure of aminoalanine moieties for intracellular bacteria targeting. Reproduced with permission from ref. (848). Copyright 2022, Wiley-VCH.

Figure 61

Synergistic polymeric nanoparticles designed to eliminate biofilms through the release of the antibiotic gentamicin and the production of bactericidal nitric oxide (A). The nanoparticles (Poly-Gen-NO) displayed outstanding antibiofilm properties including biofilm mass reduction (B) and elimination of biofilm viability (C). Reproduced with permission from ref. (865). Copyright 2016, Royal Society of Chemistry.

Figure 62

A dual-responsive nanoparticle that encapsulates the antibiotic rifampicin and preferentially targets antibiotic resistant bacteria. At the bacterial infection site, the nanoparticle’s pH- and redox-responsive behavior released both rifampicin and toxic cationic polymer fragments. This nanoparticle eliminated rifampicin-resistant bacteria 40 times more efficiently than the unencapsulated drug. Reproduced with permission from ref. (874). Copyright 2021, Wiley-VCH.

Figure 63

(A) A schematic representation of the preparation of gastricepithelial cell membrane-functionalized PLGA nanoparticles (AGS-NP) that preferentially targets H. pylori bacteria and release of antibiotic payload resulting in enhanced antibacterial efficacy. (B) TEM image of AGS-NP. (C) In vitro bactericidal activity of free clarithromycin (CLR), CLR-loaded PEGylated nanoparticle (PEG-NP (CLR)), CLR-loaded AGS-NP (AGS-NP (CLR)) ; the AGS-NP - loaded with the antibiotic CLR, was able to eliminate H. Pylori far more efficiently than either the free drug or PEGylated nanoparticle (PEG-NP), due to radically enhanced bacterial targeting. Reproduced with permission from ref. (881). Copyright 2018, Wiley-VCH.

Figure 64

A pH-responsive nanoparticle comprising an antibiotic drug–polymer conjugate for the enhanced treatment of chronic lung infections. The endogenous pH-induced release yielded smaller drug–polymer conjugate cationic nanoparticles that yielded strong biofilm penetration and bacteria elimination, as well as reduced inflammation. DA refers to DMMA. Reproduced with permission from ref. (888). Copyright 2020, American Chemical Society.

Figure 65

(A) A schematic illustration of a targeted anti-inflammatory nanoparticle (Col-IV IL-10 NP (NP22)) formulated via self-assembly of a blend of NH₂-PLGA-NH₂, PDLA-b-PEG-OMe, PLGA-b-PEG-Col IV, and IL-10. (B) The targeted nanoparticles were able to enter the atherosclerotic plaque via leaky endothelial junctions and bind to the exposed collagen IV (Col IV). The IL-10 payload was released within the plaque in a controlled manner, resulting in increased efferocytosis, an improvement in the fibrous cap size, and a decrease in necrotic core size. Reproduced with permission from ref. (911). Copyright 2016, American Chemical Society.

Figure 66

A schematic representation for the preparation of ASO-loaded glycosylated-polyion complex (GLU-PIC) micelles via self-assembly of mixture of MeO-PEG-b-PLL(MPA/IM) and glycosylated PEG-b-PLL(MPA/IM) (GLU-PEG-b-PLL(MPA/IM). The rapid increase in blood glucose level was achieved by injecting the glucose solution into overnight-fasting mice to trigger GLUT1 translocation, and GLU-PIC micelles were then intravenously administered to enhance the brain accumulation via GLUT1-mediated transcytosis. The rapid increase in blood glucose level can boost the BBB crossing of the micellar nanoparticles while improving ASO delivery to the brain. Reproduced with permission from ref. (926). Copyright 2020, Wiley-VCH.

Figure 67

Hyperbranched polymer nanoparticles for ¹⁹F MRI. The nanoparticles were functionalized with perfluoropolyether for increased fluorine content as well as a tumor targeting aptamer, yielding sensitive in vivo¹⁹F MRI capability. Reproduced with permission from ref. (945). Copyright 2018, American Chemical Society.

Figure 68

A schematic illustration of enzyme-responsive biodegradable theranostic nanoparticles via self-assembly of branched PHPMA, containing Gd(III)-complexed DOTA side chains (GD-DOTA). Enzyme responsiveness was introduced through the peptide GFLG. After tumor cell uptake, the nanoparticles are capable of acting as MRI contrast agents. Reproduced with permission from ref. (953). Copyright 2020, Wiley-VCH.

Figure 69

A luminescent nanoparticle based on aggregated-induced emission (AIE). These nanoparticles had a high photothermal conversion due to the twisting capability of the loaded fluorophore, and the nanoparticle was able to produce ROS, yielding strong anti-tumor performance. Reproduced with permission from ref. (977). Copyright 2019, Wiley-VCH.

Figure 70

Schematic synthesis route of MOF-polymer conjugates (⁸⁹Zr-UiO-66/Py-PGA-PEG-F3) and the PET imaging. Intrinsically radioactive MOF (⁸⁹Zr-UiO-66) was produced through the incorporation of positron-emitting isotope zirconium-89 (⁸⁹Zr), and further modified with Py-PEG and conjugated with an F3 peptide ligand. DOX was loaded onto MOF to serve as a both therapeutic cargo and a flurosecence visualizer. Reproduced with permission from ref. (998). Copyright 2019, Americal Chemical Society.

Figure 71

Polymeric nanoparticles offer enormous advantages as drug-delivery vehicles compared to other vectors, including tunable size and shape, highly specific targeting, stimuli-responsiveness and efficient drug loading—to name a few. There are, however, a number of challenges preventing their smooth clinical transition, including their inherent complexity, high cost, scalability issues, and a lack of clear comparisons with other drug-delivery technology, such as lipid particles.