Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy
Abstract
:1. Introduction
Statement of Significance
2. General Aspects on Designing and Fabricating Polymersomes
2.1. Choice of Polymer Type
2.2. Fabrication Techniques
2.3. Drug Loading
3. Advantages and Limitations of Polymersomes as Compared with Those of Liposomes
4. Stimuli Responsiveness of Polymersomes
4.1. pH Responsiveness
- (i)
- Protonation/deprotonation: at different pH values, the ionizable groups within the material can accept or donate protons (H+ ions), leading to a change in their charge state. This change can alter the material’s solubility, leading to disassembly or swelling of the carrier, and thus the release of the encapsulated drug [96].
- (ii)
- Hydrolysis: certain chemical bonds within the material may be stable at neutral pH but become susceptible to hydrolysis under acidic conditions. This can lead to the degradation of the material and subsequent drug release [97].
- (iii)
- Conformational change: polymers may undergo a change in their conformation in response to pH, transitioning between expanded and collapsed states. This shift can expose or hide drug molecules, controlling their release based on the environmental pH [98].
4.2. Temperature Responsiveness
4.3. Reduction Responsiveness
4.4. Enzyme Responsiveness
- (i)
- (ii)
- (iii)
- At the link between the hydrophilic brush and hydrophobic membrane: the junctions between these two structural components are crucial for the polymersome’s architecture. Enzymatic cleavage here can lead to a significant alteration in the polymersome’s configuration, directly impacting drug release rates and profiles [118,119].
4.5. Hypoxia Responsiveness
4.6. Light Responsiveness
5. Multi-Responsive Polymersomes for Cancer Therapy
6. Prospects and Challenges of Polymersomes for Clinical Development and Personalized Medicine
7. Conclusions and Future Perspectives
- (a)
- Enhanced targeting and specificity: the ongoing research aims to increase the specificity of polymersomes towards cancer cells, while minimizing their impact on healthy tissues. Advanced targeting strategies, which involve the use of tumor-specific ligands or antibodies, are expected to improve selective drug delivery, reducing side effects and enhancing therapeutic outcomes.
- (b)
- Combination therapies: polymersomes offer the unique advantage of codelivering multiple therapeutic agents, including chemotherapeutics, genes, and immunotherapies. Future developments will focus on optimizing these combination therapies to synergistically target cancer cells, overcome drug resistance, and elicit stronger immune responses.
- (c)
- Smart release mechanisms: the development of sophisticated release mechanisms which simultaneously respond to multiple stimuli or in a sequential manner will provide a fine control over drug release kinetics. This could enable the delivery of therapeutics at the optimal time and site of action within the tumor microenvironment.
- (d)
- Personalized medicine: the adaptability of polymersomes makes them ideal candidates for personalized medicine. Future research could focus on designing customized polymersomes to the molecular profile of an individual’s tumor, providing tailored therapies which offer improved efficacy and safety profiles.
- (e)
- Biocompatibility and safety: as the clinical translation of polymersomes advances, ensuring their biocompatibility and safety remains a key aspect. Future studies will need to thoroughly assess the long-term effects of polymersome administration, including their degradation products and the human body’s ability to clear them, in order to meet regulatory standards.
- (f)
- Clinical translation and scalability: efforts to translate polymersomes from the laboratory to the clinic will involve overcoming challenges related to large-scale manufacturing, stability, and storage. Developing cost-effective and scalable production methods will be crucial for making these innovative treatments accessible to a wider population.
- (g)
- Regulatory parties: it is essential to establish clear regulatory pathways for the approval of polymersome-based therapies. Collaboration between researchers, industry, and regulatory agencies will be necessary to bring these novel treatments to market.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Method | Advantages | Disadvantages | Ref. |
---|---|---|---|
Film rehydration |
|
| [56] |
Electroformation |
|
| [57] |
Solvent displacement |
|
| [58] |
Sonication |
|
| [59] |
Microfluidics |
|
| [60] |
Self-assembly in selective solvents |
|
| [61] |
Method | Details | Advantages | Disadvantages | Ref. |
---|---|---|---|---|
Extrusion |
|
|
| [76] |
Electroporation |
|
|
| [77] |
Ultrasonication |
|
|
| [78] |
Passive loading |
|
|
| [79] |
Cosolvent evaporation |
|
|
| [71] |
Diffusion |
|
|
| [15] |
Polymersome | Responsiveness | Encapsulated Drug(s) | Targeted Cancer Type | Outcomes | Ref. |
---|---|---|---|---|---|
mPEG-b-PNIPAM-b-P(DEAEMA-co-BMA) | pH + temperature | DOX and PTX | Breast and cervical cancer |
| [146] |
PVCL10-PDMS65-PVCL10 | DOX | Cancer therapy |
| [147] | |
UCNP-PNSP@DOX | Ultraviolet + redox | DOX | Non-small-cell lung cancer |
| [148] |
BCP1–3Psomes 1.PEG-b-P(FcMA-co-DEAEMA-co-DMIBM) 2.PEG-b-P(FcMA-co-DEAEMA-co-DMIHMA) 3.PEG-b-P(FcMA-co-DEAEMA-co-BPMA) | pH + redox | β-cyclodextrin | Cancer therapy |
| [149] |
BG-DIP | pH + hyperthermia | ICG and DOX | Breast cancer |
| [150] |
HO-Se-Se(dSe)-PEG-PC7A-P(BAEMA-(AEMA-SS-DOX) | pH + redox | D-peptide antagonist (DPPA-1), talabostat, and DOX | Mammary carcinoma |
| [151] |
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Negut, I.; Bita, B. Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy. Pharmaceutics 2024, 16, 463. https://doi.org/10.3390/pharmaceutics16040463
Negut I, Bita B. Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy. Pharmaceutics. 2024; 16(4):463. https://doi.org/10.3390/pharmaceutics16040463
Chicago/Turabian StyleNegut, Irina, and Bogdan Bita. 2024. "Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy" Pharmaceutics 16, no. 4: 463. https://doi.org/10.3390/pharmaceutics16040463
APA StyleNegut, I., & Bita, B. (2024). Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy. Pharmaceutics, 16(4), 463. https://doi.org/10.3390/pharmaceutics16040463