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Cell membrane inspired nano-shell enabling long-acting Glucose Oxidase for Melanoma starvation therapy via
Yang Zeng1, Haiyan Zhou2, Jinsong Ding1
1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, China.
Abstract:
Rationale: Glucose oxidase (GOx) has gained tremendous research interest recently as a glucose-consuming enzyme for tumor starvation therapy, while its in vivo applications are strictly limited by rapid deactivation, as well as side effects of non-specific catalysis. Methods: To address these issues, here we report a protective nano-shell to encapsule GOx for localized melanoma therapy delivered by dissolving microneedles (MNs). Inspired by cell membrane that separates and protects cell organelles and components from outside environment while selectively ingesting nutrition sources, we designed polydopamine (PDA)-structured nano-shell to allow free transportation of glucose for catalytic reaction, while impede the penetration of GOx, proteinase, and other GOx-deactivating macromolecules across the shell membrane. Results: GOx was well protected in core layer with persistent catalytic activity for at least 6 d under various biological matrixes (e.g., PBS, serum, and cell lysate) and surviving different harsh conditions (e.g., acid/base treatments, and proteinase-induced degradation). Such long-acting nano-catalyst can be easily integrated into MNs as topical delivery carrier for effective glucose consumption in melanoma tissue, achieving significant tumor growth inhibition via starvation therapy with minimized side effects as compared to systemic administration. Conclusion: This work provides an elegant platform for in vivo delivery of GOx, and our cell-mimicking nano-system can also be applied for other enzyme-based therapeutics.
Insights
This study developed a protective nano-shell for glucose oxidase (GOx) enzyme delivery via microneedles. The nano-shell preserves GOx activity for tumor starvation therapy, enhancing melanoma treatment with fewer side effects.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Glucose oxidase (GOx) shows promise for tumor starvation therapy but suffers from rapid deactivation and side effects in vivo.
- Current limitations hinder the clinical application of GOx for cancer treatment.
Purpose of the Study:
- To develop a protective nano-shell for encapsulating GOx to enhance its stability and efficacy for localized melanoma therapy.
- To investigate the use of dissolving microneedles (MNs) for topical delivery of the GOx-loaded nano-system.
Main Methods:
- A polydopamine (PDA)-structured nano-shell was designed to encapsulate GOx, mimicking cell membrane functions for selective transport.
- The nano-encapsulated GOx was integrated into dissolving microneedles for localized delivery to melanoma tissue.
- Stability and catalytic activity of GOx were assessed under various biological conditions and harsh treatments.
Main Results:
- The PDA nano-shell effectively protected GOx, maintaining its catalytic activity for over 6 days in diverse biological environments.
- The nano-system demonstrated resistance to proteinase degradation and harsh pH conditions.
- Microneedle-delivered GOx significantly inhibited melanoma tumor growth through starvation therapy with reduced side effects compared to systemic administration.
Conclusions:
- The developed cell-mimicking nano-system provides an effective platform for in vivo delivery of GOx, overcoming its limitations for enzyme-based therapeutics.
- This approach offers a promising strategy for localized cancer therapy, particularly for melanoma, with improved safety and efficacy.
- The nano-system design has potential applications for other enzyme-based therapeutic strategies.
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