Co-Delivery of Precisely Prescribed Multi-Prodrug Combination by an Engineered Nanocarrier enables Efficient
Yuqiang Li1, Yitong Jiang1, Ziyan Zheng1
1The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Abstract:
The limited anticancer drug library and the frequent occurrence of drug resistance have driven monotherapy-based cancer therapy into a difficult situation. Considering the formidable process of new drug discovery, combination therapy using currently available drugs is a potential alternative. Nevertheless, the barrier between in vitro combination screening and precise in vivo delivery remains insurmountable in the current free-drug- or nanoparticle (NP)-based combination therapy, which substantially hinders the application of combination therapy. Herein, a novel, precise drug delivery strategy to realize efficient and individualized combination therapy is proposed. Nanomedicine (NM) is engineered using a microfluidics-based mixer by combining rationally designed polymeric prodrugs of three commercial chemotherapeutics and a cascade-responsive block copolymer; the NM possesses ratiometric drug loading and synchronized drug release. In addition to quantitative drug loading and precisely controlled drug combination, consistent nanoproperties of these NPs make their in vivo fate predictable. Consequently, tumor growth and metastasis can be effectively inhibited by precisely prescribed NPs derived from in vitro combination screening. This proof-of-concept study clearly reveals the feasibility of overcoming the current drug-library limitations through precise delivery of any predetermined drug combination, facilitating translational research of individualized combination therapy.
Insights
This study introduces a novel nanomedicine strategy for precise cancer combination therapy. It enables effective in vivo delivery of predetermined drug combinations, overcoming limitations of current approaches.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Monotherapy faces challenges in cancer treatment due to limited drug options and resistance.
- Current combination therapy faces hurdles in precise in vitro to in vivo translation.
- Developing effective drug delivery systems is crucial for advancing combination cancer therapy.
Purpose of the Study:
- To propose a novel nanomedicine strategy for efficient and individualized cancer combination therapy.
- To overcome the limitations of current combination therapy delivery systems.
- To demonstrate the feasibility of precise in vivo delivery for predetermined drug combinations.
Main Methods:
- Engineered nanomedicine (NM) using a microfluidics-based mixer.
- Combined rationally designed polymeric prodrugs of three chemotherapeutics with a cascade-responsive block copolymer.
- Achieved ratiometric drug loading and synchronized drug release with consistent nanoproperties.
Main Results:
- Demonstrated quantitative drug loading and precisely controlled drug combinations.
- Showcased predictable in vivo behavior of the engineered nanoparticles (NPs).
- Effectively inhibited tumor growth and metastasis using precisely prescribed NPs.
Conclusions:
- The proposed nanomedicine strategy enables precise delivery of predetermined drug combinations.
- This approach facilitates overcoming limitations of current drug libraries and enhances combination therapy applications.
- The study provides a proof-of-concept for translational research in individualized cancer therapy.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:16Drug Delivery: Overview
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...