Deliver on a Promise: Hydrogen-Bonded Polymer Nanomedicine with a Precise Ratio of Chemodrug and Photosensitizer for Intelligent Cancer Therapy

Abstract

The outcomes of combined cancer therapy are largely related to loading content and contribution of each therapeutic agent; however, fine-tuning the ratio of two coloaded components toward precise cancer therapy is a great challenge and still remains in its infancy. We herein develop a supramolecular polymer scaffold to optimize the coloading ratio of chemotherapeutic agent and photosensitizer through hydrogen-bonding (H-bonding) interaction, for maximizing the efficacy of intelligent cancer chemo/photodynamic therapies (CT/PDT). To do so, we first synthesize a thymine (THY)functionalized tetraphenylporphyrin photosensitizer (i.e., TTPP), featuring the same molecular configuration of Hbonding array with chemotherapeutic carmofur (e.g., 1-hexylcarbamoyl-5-fluorouracil, HCFU). Meanwhile, a six-arm starshaped amphiphilic polymer vehicle P(DAPA-co-DPMA-co-OEGMA) 6 (poly(diaminopyridine acrylamide-co-2-(diisopropylamino)ethyl methacrylate-co-oligo(ethylene glycol) monomethyl ether methacrylate) 6 ) is prepared, bearing hydrophilic and biocompatible POEGMA segment, along with hydrophobic PDAPA and PDPMA segments, characterizing the randomly dispersed dual functionalities, i.e., heterocomplementary H-bonding DAP motifs and pH-responsive protonation DPMA content. Thanks to the identical DAP/HCFU and DAP/TTPP H-bonding association capability, the incorporation of both HCFU and TTPP to six-arm star-shaped P(DAPA-co-DPMA-co-OEGMA) 6 vehicle, with an optimized coloading ratio, can be straightforwardly realized by adjusting the feeding concentrations, thus yielding the hydrogen-bonded supramolecular nanoparticles (i.e., HCFU-TTPP-SPNs), demonstrating the codelivery of two components with the promise to optimize the combined CT/PDT efficacy.

Hydrogen bonding enhanced drug–polymer interaction for efficient drug loading and delivery

“…28–31 Following this approach, various nucleobase analogues containing polymers have been designed and synthesized by functionalizing the side-chain with diaminotriazine, diacylaminopyridine, etc. 32–36 Noteworthily, complexation between uracil and diacylaminopyridine has attracted particular interest due to their unique triple hydrogen-bonding configuration. 37,38 Taking advantage of this robust hydrogen bond, diacylaminopyridine incorporated polymers are expected to serve as promising carriers with high drug loading content and superb loading efficiency for uracil-based drugs.…”