Programmable Nanostructure Assembly of a Paclitaxel Derivative Enables Tunable Anticancer Therapy via Hydrogen Bond...

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Nanomedicine

Background:

• Precise control over self-assembling drug morphology is crucial for optimizing pharmacokinetics and therapeutic efficacy.
• Tailoring a single drug's structure for diverse therapeutic applications presents a significant challenge.

Purpose of the Study:

• To develop a hydrogen-bond-guided strategy to program the morphology of a paclitaxel derivative (PTP).
• To demonstrate how tunable hydrogen bonding enables precise programming of drug assembly morphology for tailored pharmacological performance.

Main Methods:

• A paclitaxel derivative (PTP) was modified with a phosphate group to promote supramolecular organization via hydrogen bonding.
• PTP nanofibers were coassembled with polyethylene glycol 400 (PEG) to form spherical nanoparticles (PTP@PEG) or with hyaluronic acid (HA) to form bundled fibers (PTP@HA).

Main Results:

• PTP@PEG enhanced systemic circulation, reduced renal accumulation, and improved antitumor efficacy in a murine breast cancer model.
• PTP@HA exhibited sustained release and potent therapeutic effects in a peritoneal metastasis model of colorectal cancer.
• The tunable hydrogen bonding strategy allowed for precise programming of drug assembly morphology.

Conclusions:

• This work presents a versatile platform for expanding the therapeutic applications of a single drug across multiple diseases by tuning its nanostructure.
• Utilizing simple excipients and hydrogen bonds to tune drug nanostructure offers a simple and effective approach compared to designing new carriers.