Orally delivered legumain-activated nanovehicles improve tumor accumulation and penetration for combinational photothermal-chemotherapy

Jing Wang; Yuqi Wang; Haiqiang Cao; Hong Wang; Jie Li; Youxin Li; Yaping Li; Zhiwen Zhang

doi:10.1016/j.jconrel.2020.04.019

Orally delivered legumain-activated nanovehicles improve tumor accumulation and penetration for combinational photothermal-chemotherapy

J Control Release. 2020 Jul 10:323:59-70. doi: 10.1016/j.jconrel.2020.04.019. Epub 2020 Apr 11.

Authors

Jing Wang¹, Yuqi Wang², Haiqiang Cao², Hong Wang², Jie Li², Youxin Li³, Yaping Li⁴, Zhiwen Zhang⁵

Affiliations

¹ State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, Yantai University, Yantai 264005, Shandong, China.
² State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ School of Pharmacy, Yantai University, Yantai 264005, Shandong, China.
⁴ State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, Yantai University, Yantai 264005, Shandong, China. Electronic address: ypli@simm.ac.cn.
⁵ State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong 264000, China. Electronic address: zwzhang0125@simm.ac.cn.

PMID: 32289329
DOI: 10.1016/j.jconrel.2020.04.019

Abstract

Oral chemotherapy offers a more convenient treatment option for cancer patients but the effectiveness is significantly hindered by the limited drug delivery efficiency. Herein, we designed legumain-activable melittin (LM) decorated polymeric nanovehicles loading IR-780 and sorafenib (LPN) to enhance their oral delivery to tumors, with efficient accumulation and penetration capacity, for combinational photothermal-chemotherapy of gastric cancer. The nanosized LPN displayed good stability in simulated gastrointestinal fluids. After oral administration, the oral bioavailability of sorafenib was remarkably improved (75.9-fold by LPN versus free drug suspension). Moreover, the orally administered LPN could preferentially accumulate at the tumor site and penetrate into the interior regions of the tumor mass. Upon combination with laser irradiation, LPN produced notable inhibition of tumor growth, which was more effective than the counterpart unmodified nanovehicles. Therefore, LPN represents an encouraging oral delivery nanoplatform with favorable tumor accumulation and penetration capability for oral combinational cancer therapy.

Keywords: Melittin; Nanovehicle; Oral delivery; Tumor penetration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Cysteine Endopeptidases
Drug Delivery Systems
Humans
Neoplasms* / drug therapy

Substances

Antineoplastic Agents
Cysteine Endopeptidases
asparaginylendopeptidase