Issue 24, 2020

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

Abstract

Most cancer chemotherapy regimens rely on the use of two or more chemotherapeutic agents. However, achieving the best possible dosing of the individual drugs can be challenging due to differences in metabolism, uptake, and clearance among other factors. Here we describe a supramolecular strategy for achieving drug delivery in which the loading ratio of two active components is easily defined. Specifically, we report the formation of aggregates comprised of self-assembled amphiphiles between carboxylatopillar[6]arene (CP6A) and an oxaliplatin (OX)-type Pt(IV) prodrug (PtC10). The association constant (Ka) for the underlying host–guest interaction at pH 7.4 ((1.16 ± 0.03) × 104 M−1) is an order of magnitude higher than at pH 5.0 ((1.73 ± 0.15) × 103 M−1). A second chemotherapeutic, doxorubicin (DOX), may be encapsulated in the resulting vesicles (PtC10⊂CP6A) to give a supramolecular combination chemotherapeutic system DOX@PtC10⊂CP6A. Drug release studies served to confirm that PtC10 and DOX are released in acidic environments. Support for a synergistic antiproliferative effect relative to PtC10 + DOX came from cellular studies of DOX@PtC10⊂CP6A using the human liver hepatocellular carcinoma (HepG-2) cell line. In vivo studies revealed that DOX@PtC10⊂CP6A is not only able to retard tumor growth efficiently but also reduce drug-related toxic side effects in BALB/c nude mice bearing HepG-2 subcutaneous tumor xenografts. These favorable findings are attributed to the formation of a ternary complex that benefits from an enhanced permeability and retention (EPR) effect in vivo while allowing for the pH-based release of PtC10 and DOX at the tumor site.

Graphical abstract: Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

Supplementary files

Article information

Article type
Edge Article
Submitted
26 Marts 2020
Accepted
01 Jūn. 2020
First published
03 Jūn. 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2020,11, 6275-6282

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

J. Chen, Y. Zhang, Z. Meng, L. Guo, X. Yuan, Y. Zhang, Y. Chai, J. L. Sessler, Q. Meng and C. Li, Chem. Sci., 2020, 11, 6275 DOI: 10.1039/D0SC01756F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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