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Transdermal siRNA delivery by pH-switchable micelles with targeting effect suppress skin melanoma progression
Mao-Ze Wang1, Jie Niu1, Hui-Jian Ma1
1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Abstract:
Melanoma is an aggressive disease with rapid progression and fast relapse, representing one of the formidable challenges in clinic. Current systemic therapies for melanoma exhibit limited anticancer potential due to the lack of specificity and limited efficacy. Herein, we design a cationic polymer (SCP-HA-PAE) by conjugating skin/cell penetrating peptide (SCP) and hyaluronic acid (HA) to the amphipathic polymer (poly β-amino esters, PAE), then fabricate the nanocarriers (SHP) composed by SCP-HA-PAE for delivering siRNA to skin melanoma by transdermal application. SHP not only manifests the excellent ability in penetrating through skin stratum corneum (SC), targeting melanoma and being sensitive to pH, but also expresses the advantages in compacting the vector/siRNAs nanocomplexes and stimulating their endosome escape inside cells, which ensure the enhanced siRNA delivery efficiency. SHP/siRNA induce the strong efficacy in retarding the progression and relapse of skin melanoma through the enhanced apoptosis effect both in vitro & in vivo. This study provides a proof-of-concept design of pH-switchable cationic micelles as transdermal gene delivery nanoplatforms with targeting effect for melanoma therapy, which may be adapted widely in the treatment of various superficial tumors and skin genetic diseases.
Insights
Researchers developed novel nanocarriers (SHP) for transdermal siRNA delivery to treat skin melanoma. These nanocarriers effectively target melanoma, enhance siRNA delivery, and show strong efficacy in reducing tumor progression and relapse.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Dermatology
Background:
- Melanoma is an aggressive skin cancer with limited treatment options.
- Current therapies lack specificity and efficacy, leading to rapid progression and relapse.
- There is a need for targeted and effective delivery systems for melanoma treatment.
Purpose of the Study:
- To design and fabricate novel nanocarriers (SHP) for transdermal delivery of siRNA to skin melanoma.
- To evaluate the efficacy of SHP/siRNA in targeting melanoma and inhibiting tumor growth.
- To establish a proof-of-concept for pH-switchable cationic micelles in transdermal gene therapy.
Main Methods:
- Conjugation of skin/cell penetrating peptide (SCP) and hyaluronic acid (HA) to poly β-amino esters (PAE) to form SCP-HA-PAE.
- Fabrication of nanocarriers (SHP) for siRNA delivery.
- In vitro and in vivo evaluation of skin penetration, melanoma targeting, pH-sensitivity, endosome escape, and therapeutic efficacy.
Main Results:
- SHP demonstrated excellent skin penetration, melanoma targeting, and pH-sensitivity.
- The nanocarriers effectively compacted siRNA and facilitated endosome escape, enhancing delivery efficiency.
- SHP/siRNA significantly retarded skin melanoma progression and relapse by inducing apoptosis in vitro and in vivo.
Conclusions:
- pH-switchable cationic micelles (SHP) serve as effective transdermal gene delivery nanoplatforms for melanoma therapy.
- This approach shows potential for treating superficial tumors and skin genetic diseases.
- The study provides a promising strategy for advanced melanoma treatment via targeted siRNA delivery.
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