Photoreactive Mercury-Containing Metallosupramolecular Nanoparticles with Tailorable Properties That Promote Enhanced Cellular Uptake for Effective Cancer Chemotherapy

Abstract

A new potential route to enhance the efficiency of supramolecular polymers for cancer chemotherapy was successfully demonstrated by employing a photosensitive metallosupramolecular polymer (Hg-BU-PPG) containing an oligomeric poly(propylene glycol) backbone and highly sensitive pH-responsive uracil-mercury-uracil (U-Hg-U) bridges. This route holds great promise as a multifunctional bioactive nano-object for development of more efficient and safer cancer chemotherapy. Owing to the formation of uracil photodimers induced by ultraviolet irradiation, Hg-BU-PPG can form a photo-cross-linked structure and spontaneously forms spherical nanoparticles in aqueous solution. The irradiated nanoparticles possess many unique characteristics, such as unique fluorescence behavior, highly sensitive pH-responsiveness, and intriguing phase transition behavior in aqueous solution as well as high structural stability and antihemolytic activity in biological media. More importantly, a series of cellular studies clearly confirmed that the U-Hg-U photo-cross-links in the irradiated nanoparticles substantially enhance their selective cellular uptake by cancer cells via macropinocytosis and the mercury-loaded nanoparticles subsequently induce higher levels of cytotoxicity in cancer cells (compared to non-irradiated nanoparticles), without harming normal cells. These results are mainly attributed to cancer cell microenvironment-triggered release of mercury ions from disassembled nanoparticles, which rapidly induce massive levels of apoptosis in cancer cells. Overall, the pH-sensitive U-Hg-U photo-cross-links within this newly discovered supramolecular system are an indispensable factor that offers a potential path to remarkably enhance the selective therapeutic effects of functional nanoparticles toward cancer cells.

Hydrogen-Bonding Interactions from Nucleobase-Decorated Supramolecular Polymer: Synthesis, Self-Assembly and Biomedical Applications

“…Metallosupramolecular coordination polymers through hydrogen bonding interaction from the nucleobase provide unique physical properties including pH sensitivity and tunable structural features due to the presence of hydrogen-bonded nucleobase moieties. For instance, uracil–mercury–uracil (U–Hg–U) and (Cy-Ag-Cy) linkages within supramolecular polymers exhibited extraordinarily blue fluorescence behavior due to extended conjugation of the U/C moieties providing stable sp 2 orbitals that overlap with the π-systems, which is promising for bioimaging. ,, These metallosupramolecular polymeric nanoclusters paved the way for the fabrication of imaging agents that can be effectively used for diagnosis purposes without the need for additional fluorescent probes.…”

“…A further investigation carried out by the same group revealed that photoreactive mercury-containing metallosupramolecular polymer (U−Hg− U) undergo UV irradiated photo-cross-linking in aqueous solution and the resulting nanoparticle achieved rapid cellular internalization into solid tumors reiterating the prospect of selfassembled supramolecular polymers as a promising platform for efficient cancer chemotherapy. 113 4.2. Bioimaging.…”

“…For instance, uracil−mercury−uracil (U− Hg−U) and (Cy-Ag-Cy) linkages within supramolecular polymers exhibited extraordinarily blue fluorescence behavior due to extended conjugation of the U/C moieties providing stable sp 2 orbitals that overlap with the π-systems, which is promising for bioimaging. 100,101,113 These metallosupramolecular polymeric nanoclusters paved the way for the fabrication of imaging agents that can be effectively used for diagnosis purposes without the need for additional fluorescent probes.…”

“…These metallo-supramolecular materials demonstrated selective uptake via endocytosis into cancer cells by massive apoptotic cell death without requiring the incorporation of anticancer drugs. A further investigation carried out by the same group revealed that photoreactive mercury-containing metallosupramolecular polymer (U–Hg–U) undergo UV irradiated photo-cross-linking in aqueous solution and the resulting nanoparticle achieved rapid cellular internalization into solid tumors reiterating the prospect of self-assembled supramolecular polymers as a promising platform for efficient cancer chemotherapy …”

Amphiphilic Block Copolymers Containing Benzenesulfonyl Azide Groups as Visible Light-Responsive Drug Carriers for Image-Guided Delivery

“…Over the past few decades, various nanoparticles (NPs) have been developed specifically for cancer treatment. 2,3 However, many early NPs failed to demonstrate satisfactory pharmaceutical outcomes clinically due to various limitations and obstacles. 4−9 These limitations include a short plasma half-life, inconsistent drug encapsulation efficiency (EE), erratic drug release, limited membrane permeability, systemic toxicity, and drug resistance.…”