Near-Infrared Photo-controlled Permeability of a Biomimetic Polymersome with Sustained Drug Release and Efficient Tumor Therapy

Abstract

Synthetic polymersomes have structure similarity to biovesicles and could disassemble in response to stimuli for "on-demand" release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and in vivo. This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

“…In an example of simultaneous photoconversion with UCNPs and photocleavage for multiple therapies, He and collaborators developed a nanoreactor based on oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) mixed with synthetically derived eosin Y (derived EoS) and ONB oxycarbonyl aminoethyl methacrylate (NBOC) hydrophobic monomer with an ONB photolabile group ( Figure 12 ) [ 303 ]. The resulting amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC (POPN) was synthesized via RAFT polymerization.…”

“… Schematic illustration of ( a ) amphiphilic copolymer POPN, ( b ) polymersome self-assembly with a permeability conversion mechanism, and ( c ) mitochondrion location and the intracellular delivery of AQ4N and PDT activated by NIR. Reprinted with permission from [ 303 ]. Copyright © 2022, American Chemical Society.…”

Polymersomes: Soft Nanoparticles from Miktoarm Stars for Applications in Drug Delivery

“…16 To increase their versatility in polymersome compositions, block copolymers have been combined with low molecular weight compounds or biomolecules 38 or substituted with amphiphilic homopolymers, polypeptides, glycoproteins, starch, polycarbonates, graft copolymers, 4,50 and bottlebrush polymers. 51 In addition to drug delivery, and because of the high stability and similarity in structure to cell membranes, polymersomes have also been investigated for biomedical applications including gene therapy, 52 magnetic resonance imaging (MRI), 53 artificial organelles, 54 protocellular constructs, 55 tumor therapy, 56 bacteria inhibition, 57 anti-inflammation, 58 active surfaces, 59 cancer theranostics, 5 and cell mimicking. 60 Their utility has also been expanded to fields such as compartments for nanoscale in situ reactions and nanoreactors, 61,62 nanodevices, 63 nanosensors, 64 catalysis, 65 and water treatment.…”

Feasibility of Using Poly[oligo(ethylene glycol) Methyl Ether Methacrylate] as Tumor-Targeted Carriers of Diagnostic Drugs

“…The grafted EG chains drastically improve the water solubility and biocompatibility of methacrylate polymers, facilitating the broad adoption of POEGMA in the biomedical field . Similar to poly­(ethylene glycol) (PEG), POEGMA is often conjugated to various therapeutic agents, including peptides, proteins, , and nanoparticles, − which can prevent immunogenicity and improve the circulation half-life of these therapeutic materials, leading to enhanced therapeutic efficacy. In particular, micelles composed of amphiphilic block polymers of hydrophilic POEGMA and hydrophobic polymers have been extensively investigated in the field of drug delivery aiming at tumor-targeted theranostics (therapy + diagnosis). − Gao et al also reported the conjugation of POEGMA and proteins (green fluorescence protein; GFP) with improved stability and tumor uptake by CT26 tumors. , …”