Therapeutic Supramolecular Polymers: Designs and Applications

Overview

Journal Prog Polym Sci

Publisher Elsevier

Date 2024 Jan 8

PMID 38188703

Authors

Han Wang

Jason Mills

Boran Sun

Honggang Cui

Affiliations

Soon will be listed here.

Abstract

The self-assembly of low-molecular-weight building motifs into supramolecular polymers has unlocked a new realm of materials with distinct properties and tremendous potential for advancing medical practices. Leveraging the reversible and dynamic nature of non-covalent interactions, these supramolecular polymers exhibit inherent responsiveness to their microenvironment, physiological cues, and biomolecular signals, making them uniquely suited for diverse biomedical applications. In this review, we intend to explore the principles of design, synthesis methodologies, and strategic developments that underlie the creation of supramolecular polymers as carriers for therapeutics, contributing to the treatment and prevention of a spectrum of human diseases. We delve into the principles underlying monomer design, emphasizing the pivotal role of non-covalent interactions, directionality, and reversibility. Moreover, we explore the intricate balance between thermodynamics and kinetics in supramolecular polymerization, illuminating strategies for achieving controlled sizes and distributions. Categorically, we examine their exciting biomedical applications: individual polymers as discrete carriers for therapeutics, delving into their interactions with cells, and dynamics; and supramolecular polymeric hydrogels as injectable depots, with a focus on their roles in cancer immunotherapy, sustained drug release, and regenerative medicine. As the field continues to burgeon, harnessing the unique attributes of therapeutic supramolecular polymers holds the promise of transformative impacts across the biomedical landscape.

References

Feng Q, Wei K, Lin S, Xu Z, Sun Y, Shi P . Mechanically resilient, injectable, and bioadhesive supramolecular gelatin hydrogels crosslinked by weak host-guest interactions assist cell infiltration and in situ tissue regeneration. Biomaterials. 2016; 101:217-28. DOI: 10.1016/j.biomaterials.2016.05.043. View

MacKay J, Chen M, McDaniel J, Liu W, Simnick A, Chilkoti A . Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat Mater. 2009; 8(12):993-9. PMC: 2862348. DOI: 10.1038/nmat2569. View

Alvarez Z, Kolberg-Edelbrock A, Sasselli I, Ortega J, Qiu R, Syrgiannis Z . Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury. Science. 2021; 374(6569):848-856. PMC: 8723833. DOI: 10.1126/science.abh3602. View

Maeda H, Wu J, Sawa T, Matsumura Y, Hori K . Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000; 65(1-2):271-84. DOI: 10.1016/s0168-3659(99)00248-5. View

Black M, Trent A, Kostenko Y, Lee J, Olive C, Tirrell M . Self-assembled peptide amphiphile micelles containing a cytotoxic T-cell epitope promote a protective immune response in vivo. Adv Mater. 2012; 24(28):3845-9. DOI: 10.1002/adma.201200209. View

Liu S, Zhang P, Banerjee S, Xu J, Pomper M, Cui H . Design and assembly of supramolecular dual-modality nanoprobes. Nanoscale. 2015; 7(21):9462-6. PMC: 4618464. DOI: 10.1039/c5nr01518a. View

Chen X, Gao H, Deng Y, Jin Q, Ji J, Ding D . Supramolecular Aggregation-Induced Emission Nanodots with Programmed Tumor Microenvironment Responsiveness for Image-Guided Orthotopic Pancreatic Cancer Therapy. ACS Nano. 2020; 14(4):5121-5134. DOI: 10.1021/acsnano.0c02197. View

Wang H, Monroe M, Wang F, Sun M, Flexner C, Cui H . Constructing Antiretroviral Supramolecular Polymers as Long-Acting Injectables through Rational Design of Drug Amphiphiles with Alternating Antiretroviral-Based and Hydrophobic Residues. J Am Chem Soc. 2023; 145(39):21293-21302. PMC: 11044016. DOI: 10.1021/jacs.3c05645. View

Anderson C, Chakroun R, Grimmett M, Domalewski C, Wang F, Cui H . Collagen-Binding Peptide-Enabled Supramolecular Hydrogel Design for Improved Organ Adhesion and Sprayable Therapeutic Delivery. Nano Lett. 2022; 22(10):4182-4191. PMC: 9844543. DOI: 10.1021/acs.nanolett.2c00967. View

10.

Cheng H, Zheng R, Fan G, Fan J, Zhao L, Jiang X . Mitochondria and plasma membrane dual-targeted chimeric peptide for single-agent synergistic photodynamic therapy. Biomaterials. 2018; 188:1-11. DOI: 10.1016/j.biomaterials.2018.10.005. View

11.

Lee S, Hsu E, Mendoza M, Ghodasra J, Nickoli M, Ashtekar A . Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis. Adv Healthc Mater. 2014; 4(1):131-141. PMC: 4206675. DOI: 10.1002/adhm.201400129. View

12.

Debnath S, Roy S, Ulijn R . Peptide nanofibers with dynamic instability through nonequilibrium biocatalytic assembly. J Am Chem Soc. 2013; 135(45):16789-92. DOI: 10.1021/ja4086353. View

13.

Wen Y, Collier J . Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol. 2015; 35:73-9. PMC: 4610357. DOI: 10.1016/j.coi.2015.06.007. View

14.

Wojtecki R, Meador M, Rowan S . Using the dynamic bond to access macroscopically responsive structurally dynamic polymers. Nat Mater. 2010; 10(1):14-27. DOI: 10.1038/nmat2891. View

15.

Chen J, Fries C, Berendam S, Rodgers N, Roe E, Wu Y . Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation. Sci Adv. 2022; 8(38):eabq0273. PMC: 9506727. DOI: 10.1126/sciadv.abq0273. View

16.

Cook A, Lesterhuis W, Nowak A, Lake R . Chemotherapy and immunotherapy: mapping the road ahead. Curr Opin Immunol. 2016; 39:23-9. DOI: 10.1016/j.coi.2015.12.003. View

17.

Molla M, Prasad P, Thayumanavan S . Protein-induced supramolecular disassembly of amphiphilic polypeptide nanoassemblies. J Am Chem Soc. 2015; 137(23):7286-9. PMC: 4916839. DOI: 10.1021/jacs.5b04285. View

18.

Liu S, Zhang Q, Shy A, Yi M, He H, Lu S . Enzymatically Forming Intranuclear Peptide Assemblies for Selectively Killing Human Induced Pluripotent Stem Cells. J Am Chem Soc. 2021; 143(38):15852-15862. PMC: 8588069. DOI: 10.1021/jacs.1c07923. View

19.

Ligthart G, Ohkawa H, Sijbesma R, Meijer E . Complementary quadruple hydrogen bonding in supramolecular copolymers. J Am Chem Soc. 2005; 127(3):810-1. DOI: 10.1021/ja043555t. View

20.

Gacanin J, Hedrich J, Sieste S, Glasser G, Lieberwirth I, Schilling C . Autonomous Ultrafast Self-Healing Hydrogels by pH-Responsive Functional Nanofiber Gelators as Cell Matrices. Adv Mater. 2018; 31(2):e1805044. DOI: 10.1002/adma.201805044. View