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Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment
Huang, Xiaobei1; Mu, Ning2; Ding, Yuanfu3; Lam, Hou Wang3; Yue, Ludan3; Gao, Cheng3; Chen, Tunan2; Yuan, Zhen4; Wang, Ruibing3
2022-07-15
Source PublicationActa Biomaterialia
ISSN1742-7061
Volume147Pages:356-365
Abstract

Nanoparticles (NPs) modified with targeting ligands have often shown great potential in targeted drug delivery for tumor therapy. However, the clearance of NPs by the monocyte-phagocyte system (MPS) and the relatively low cellular uptake by tumor cells have significantly limited the antitumor efficacy of a variety of nanomedicines. Tumor microenvironment-mediated multidrug resistance also reduces the antitumor efficacy of internalized nanomedicines. Herein, we developed an innovative nanomedicine for combined chemo-photodynamic therapy of melanoma through targeted drug delivery and significantly improved the cellular uptake of the nanomedicine through the charge-reversal phenomenon. An amphiphilic platinum (IV)-polyethylenimine-chlorin e6 (Pt(IV)-PEI-Ce6) polymer was designed, prepared, and self-assembled into NPs (PPC) in an aqueous solution, and these NPs were subsequently coated with hyaluronic acid (HA) to afford PPC@HA. The surface-coated HA provided PPC with a negatively charged surface potential to reduce the clearance by the MPS during systemic circulation and enhanced the targeted delivery of PPC to CD44-overexpressing melanoma cells. Upon accumulation in the tumor site, hyaluronidase overexpressed in the tumor induced HA degradation to release the positively charged PPC, resulting in an increased internalization of PPC into tumor cells. Bioactive Pt(II) was released in response to high glutathione level in the tumor cells for effective tumor chemotherapy. Under 650 nm laser irradiation, Ce6 produced reactive oxygen species (ROS), thus driving photodynamic therapy. Finally, PPC@HA exhibited combined photodynamic-chemotherapeutic antitumor efficacy against the melanoma cells in mice. Statement of significance: Tumors are one of the greatest threats to human health, and chemotherapy has been one of the most common therapeutic modalities for treating tumors; however, many challenges related to chemotherapy remain, such as low delivery efficiency, side effects, and unsatisfactory therapeutic efficacy. Nanomedicines modified with targeting ligands have often shown great potential in improving targeted drug delivery for tumor therapy; however, the clearance of nanomaterials by the monocyte-phagocyte system and the relatively low cellular uptake by tumor cells have significantly limited the antitumor efficacy of a variety of nanomedicines. Herein, we developed a novel charge-reversal-based, hyaluronic acid-coated, Pt(IV) prodrug and chlorin e6-based nanomedicine to improve systemic circulation and targeted accumulation of the nanomedicine in the tumor tissue and to enhance its intracellular uptake. This nanomedicine may provide a potential new platform to improve the drug content inside tumor cells and to effectively inhibit tumor growth through combined chemotherapy and photodynamic therapy.

KeywordCharge-reversal Controlled Drug Release Photodynamic-chemotherapeutic Therapy Pt(Iv) Prodrug Targeted Drug Delivery
DOI10.1016/j.actbio.2022.05.015
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000829655400009
Scopus ID2-s2.0-85130569656
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Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Corresponding AuthorChen, Tunan; Yuan, Zhen; Wang, Ruibing
Affiliation1.Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, No.266 Fangzheng Avenue, Beibei District, 400714, China
2.Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, The Third Military Medical University (Army Military Medical University), Chongqing, 400038, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Avenida da Universidade, 999078, China
4.Faculty of Health Sciences, University of Macau, Taipa, Avenida da Universidade, 999078, China
Corresponding Author AffilicationFaculty of Health Sciences;  Institute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Huang, Xiaobei,Mu, Ning,Ding, Yuanfu,et al. Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment[J]. Acta Biomaterialia,2022,147:356-365.
APA Huang, Xiaobei,Mu, Ning,Ding, Yuanfu,Lam, Hou Wang,Yue, Ludan,Gao, Cheng,Chen, Tunan,Yuan, Zhen,&Wang, Ruibing.(2022).Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment.Acta Biomaterialia,147,356-365.
MLA Huang, Xiaobei,et al."Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment".Acta Biomaterialia 147(2022):356-365.
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