Cancer is one of the leading causes of death worldwide, and a great deal of effort has been put into discovering and developing effective cancer** methods. Nanomedicine, a method to improve clinical performance and reduce undesirable properties, has been extensively studied to enable high-performance cancer-specific drug applications. Single chemotherapy drugs are often limited by systemic toxicity and resistance, so researchers have developed methods to co-pack two or more drugs in a single vehicle to achieve the effect of combination**. However, the chemical structure, function, and performance of each drug are different, and in order to take full advantage of each of their respective advantages and optimize the final anti-tumor effect, there is an urgent need to achieve finely controlled multi-drug loads in precise proportions.
In this regard,School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyZhu JintaoProfessorsChen SenbinResearcherTeamA hydrogen-bonded polymer with precise ratios of chemical drugs and photosensitizers for smart cancer was constructed**. The study, titled "Deliveron a Promise: Hydrogen-Bonded Polymer Nanomedicine with a Preciseratio of Chemodrug and Photosensitizer for Intelligent Cancertherapy,** was published in ACSNANO.
In this work, the Thy functionalized H-bond photosensitizer TTPP was designed and synthesized for the first time, with the same H-bond ADA array as the chemotherapy molecule HCFU (Figure 1). On the other hand, the six-armed astrophilic amphiphilic polymer P (DAPA-CO-DPMA-CO-OEGMA)6 was synthesized as a customized drug carrier with hydrophilic and biocompatible POEGMA moiegma, as well as hydrophobic PDAPA and PDPMA moiego. In this design, the PDPM** segment is characterized by a heterogeneously complementary DADH bond recognition site for the thy and HCFU motifs, while the PDPM** segment is exposed to acidic pH conditions of lysosomes (50−6.0) Can be easily geologically subgraded.
Since DAP HCFU and DAP TTPP have the same hydrogen bond interactions, HCFU and TTPP can be combined into the P(DAPA-CO-DPMA-CO-OEGMA)6 vector and an optimized and precise coloading ratio can be achieved. Therefore, by fine-tuning the loading ratio of HCFU-TTPP, H-bonded supramolecular polymer micelles, i.e., HCFU-TTPP-SPN, can be easily prepared, which has the characteristics of co-delivery of two components. The antitumor properties of HCFU-TTPP-SPNs remain dormant until they are replaced by acidic endocytic organelles (i.e., pH5.).0-6.0) Protonation decomposition of PDPMA. More importantly, HCFU-TTPP-SPN accumulates into tumor tissues through enhanced permeability and retention (EPR) effects and cellular uptake, and in vivo DAP HCFUH bond dissociation and subsequent HCFU release behavior can be achieved by a slightly lower pH of tumor cell lysosomes, without the need to add competing molecules or additionally design responsive attachment to drug vectors, which is one of the most significant differences. Thus, under 655 nm laser irradiation, reactively-released chemoHCFUs, as well as TTPP-generated ROS, can achieve a combination of the ratio between HCFU-based CT and TTPP-induced PDT** (Figure 1).
Figure 1Schematic diagram of pH-triggered drug release in vivo for CT PDT combined with anti-tumor**.
Taken together, the authors constructed an effective strategy to fabricate a nanoplatform for chemotherapeutic drug and photosensitizer co-delivery, characterized by precise co-loading of the ratio of the two components by H-bond interaction, to maximize the purpose of CT PDT in combination with cancer**. The H-bond array molecular configuration between the chemotherapy HCFU and the photosensitizer TTPP is the same, and the binding constants for heterocomplementary DAP groups are similar, which can ensure the accurate loading ratio between HCFU and TTPP in the same vehicle. Compared with linear analogues, the six-arm astropolymer carrier has the characteristics of compact structure, small hydrodynamic volume and radius of rotation, and more importantly, it has H-bond recognition sites and pH-triggered protonation groups, which indeed contributes to the formation of H-bonded nanodrugs HCFU(72%)-TTPP(28%)-SPN, and enables smart drug release mechanisms. Under 655 nm laser irradiation, HCFU(72%)-TTPP(28%)-SPN was used to determine the significant tumor growth inhibition behavior. HCFU(72%)-TTPP(28%)-SPN effectively maximizes the combined efficacy of CT PDT and makes multi-drug quantitative co-loading programmable. It is believed that this hydrogen-bonded nanomedicine with precise co-loading ratio can provide favorable cancer treatment** and help to achieve multi-drug combination.
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