Polymeric Nanoparticles Simultaneously Delivering Paclitaxel Prodrug and Combretastatin A4 with Exceptionally High Drug Loading for Cancer Combination Therapy
Nanomedicines capable of delivering multiple drugs have become essential in combination therapy. However, the challenges of low drug loading capacity (DLC) and difficulties in administering dosages between different drugs significantly limit the antitumor efficacy. In this study, a nanomedicine constructed through a rational prodrug and nanocarrier design was reported for cancer combination therapy. Initially, a phenylborate ester (PBE) group-modified paclitaxel (PTX) prodrug (PTX-PBE) was synthesized and could self-assemble in water. Subsequently, combretastatin A4 (CA4) polymer conjugates, mPEG-PCA4 (PCA4), were synthesized as nanocarriers to facilitate the exceptionally high drug loading of PTX-PBE in a precisely controlled manner. Both the <i>in vitro</i> and <i>in vivo</i> experiments demonstrated that the PCA4 loading PTX-PBE nanoparticles (PCA4/PTX-PBE NPs) exhibited potent antitumor efficacy and favorable biocompatibility. Our approach provides a straightforward, efficient, and controllable strategy for the co-delivery of pharmaceuticals in clinical cancer combination therapy.
Authors
- Liwei Mi (ORCID: https://orcid.org/0000-0001-9239-6599)
- Hai Sun (ORCID: https://orcid.org/0009-0003-3305-6238)
- Zhaofan Yang
- Yuanzhen Su (ORCID: https://orcid.org/0000-0002-6007-0655)
- Xuesi Chen (ORCID: https://orcid.org/0000-0003-3542-9256)
- Huicong Zhou
- Mingqiang Li (ORCID: https://orcid.org/0000-0002-5178-4138)
- Guan-Yu Jin
- Irina A. Veselova
- Shixian Lv (ORCID: https://orcid.org/0000-0001-5623-7224)
- Ling‐Wei Xue (ORCID: https://orcid.org/0000-0001-9346-9999)
- Hao Liu (ORCID: https://orcid.org/0000-0002-5181-7024)
- Lanqing Wang (ORCID: https://orcid.org/0000-0003-2157-4575)
Institutions
- King University (US)
- Pingdingshan University (CN)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Lomonosov Moscow State University (RU)
- Peking University (CN)
- Changchun Institute of Applied Chemistry (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Moscow State University (TJ)
Publication Details
- Journal
- Nano Letters
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1021/acs.nanolett.4c05863
- Citations
- 12
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 7.17
Funders
- National Natural Science Foundation of China
- Education Department of Jilin Province
- Guangzhou Municipal Science and Technology Project
- National Key Research and Development Program of China
- Natural Science Foundation of Guangdong Province for Distinguished Young Scholars