Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy

Abstract

This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring the potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely to tumor sites by responding to specific stimuli such as pH, temperature, light, hypoxia, and redox conditions, thereby minimizing the side effects associated with traditional chemotherapy. We discuss the design, synthesis, and recent applications of polymersomes, emphasizing their ability to improve therapeutic outcomes through controlled drug release and targeted delivery. Moreover, we highlight the critical areas for future research, including the optimization of polymersome-biological interactions and biocompatibility, to facilitate their clinical adoption. Multi-responsive polymersomes emerge as a promising development in nanomedicine, offering a pathway to safer and more effective cancer treatments.

Keywords: cancer therapy; multi-responsive polymersomes; targeted drug delivery.

Figure 1

Schematic representation of a polymersome, containing hydrophilic and hydrophobic drugs loaded within its core and membranes. The surfaces of polymersomes can be further modified with selective targeting moieties. Image created with Biorender.com (accessed on 4 March 2024).

Figure 2

Illustration of various amphiphilic copolymers and their anticipated structural arrangement within the bilayer membrane of polymersomes [27].

Figure 3

(a) Typical morphology of spherical vesicular structures with an inner hydrophilic core and outer hydrophobic shell of blank polymersomes formed at pH 7.4 with a polymer concentration of 5 mg·mL⁻¹ (scale bar = 100 nm), (b) TEM image of drug-loaded (5 wt.% Dox·HCl) polymersomes (scale bar = 100 nm) [80].

Figure 4

Advantages and limitations of polymersomes as compared with their counterparts, liposomes.

Figure 5

Cumulative in vitro release profiles of drug-loaded (10 wt.% Dox·HCl) polymersomes in PBS (10 mM, pH 7.4) with or without 50 mM GSH at 37 °C (mean ± SD, n = 3). The polymersomes exhibited a prolonged drug release behavior, with 34.3 ± 8.4% drug released at physiological pH after 48 h, attributed to their structural stability. The drug release rate increased at 50 mM GSH, with a cumulative drug release up to 77.1 ± 3.1% after 48 h. The disulfide linkages in the hydrophobic block of the copolymer were cleaved in the reductive environment, leading to the rupture of polymersomes, which subsequently accelerated drug release [80].

Figure 6

(a) Schematics for the controllable light-responsive corelease of DOX and NR drugs from the developed polymersomes of PDMA-b-PNBA. PDMA-b-PNBA: N,N′-dimethylacrylamide-b-o-nitrobenzyl acrylate; (b) (left)—emission spectra of NR for the polymersome solution without UV irradiation; (right)—emission spectra of NR for the polymersome solution under UV irradiation at 365 nm; (c) controlled release of DOX on exposure to UV light with different times [35].