2. Academic Validation
  3. Chimeric Peptide Engineered Nanomedicine for Synergistic Suppression of Tumor Growth and Therapy-Induced Hyperlipidemia by mTOR and PCSK9 Inhibition

Chimeric Peptide Engineered Nanomedicine for Synergistic Suppression of Tumor Growth and Therapy-Induced Hyperlipidemia by mTOR and PCSK9 Inhibition

  • Pharmaceutics. 2023 Sep 23;15(10):2377. doi: 10.3390/pharmaceutics15102377.
Hua Cai 1 2,  Rongrong Zheng 3,  Ningxia Wu 1 2,  Jiaman Hu 1 4,  Ruixin Wang 1,  Jianing Chi 1,  Wei Zhang 4,  Linping Zhao 3,  Hong Cheng 5,  Ali Chen 4,  Shiying Li 3,  Lin Xu 1 2
Affiliations

Affiliations

  • 1 Department of Geriatric Cardiology, General Hospital of Southern Theater Command, People's Liberation Army, Guangzhou 510010, China.
  • 2 Graduate School, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 3 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
  • 4 School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 5 Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
PMID: 37896137 DOI: 10.3390/pharmaceutics15102377
Abstract

Chemotherapy-induced side effects restrain anti-tumor efficiency, with hyperlipidemia being the most common accompanying disease to cause treatment failure. In this work, a chimeric peptide-engineered nanomedicine (designated as PRS) was fabricated for the synergistic suppression of tumor growth and therapy-induced hyperlipidemia. Within this nanomedicine, the tumor matrix-targeting peptide palmitic-K(palmitic)CREKA can self-assemble into a nano-micelle to encapsulate Rapamycin (mTOR Inhibitor) and SBC-115076 (PCSK9 Inhibitor). This PRS nanomedicine exhibits a uniform nano-distribution with good stability which enhances intracellular drug delivery and tumor-targeting delivery. Also, PRS was found to synergistically inhibit tumor cell proliferation by interrupting the mTOR pathway and reducing Rapamycin-induced hyperlipidemia by increasing the production of LDLR. In vitro and in vivo results demonstrate the superiority of PRS for systematic suppression of tumor growth and the reduction of hyperlipidemia without initiating any Other toxic side effects. This work proposes a sophisticated strategy to inhibit tumor growth and also provides new insights for cooperative management of chemotherapy-induced side effects.

Keywords

Rapamycin; anti-tumor; hyperlipidemia; nanomedicine; proprotein convertase subtilisin/kexin type 9 (PCSK9); tumor-targeted peptide.

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