Blocking
energy metabolism of cancer cells and simultaneously stimulating
the immune system to perform immune attack are significant for cancer
treatment. However, how to potently deliver different drugs with these
functions remains a challenge. Herein, we synthesized a nanoprodrug
formed by a F127-coated drug dimer to inhibit glycolysis of cancer
cells and alleviate the immunosuppressive microenvironment. The dimer
was delicately constructed to connect lonidamine (LND) and NLG919
by a disulfide bond which can be cleaved by excess GSH to release
two drugs. LND can decrease the expression of hexokinase II and destroy
mitochondria to restrain glycolysis for energy supply. NLG919 can
reduce the accumulation of kynurenine and the number of regulatory
T cells, thus alleviating the immunosuppressive microenvironment.
Notably, the consumption of GSH by disulfide bond increased the intracellular
oxidative stress and triggered immunogenic cell death of cancer cells.
This strategy can offer more possibilities to explore dimeric prodrugs
for synergistic cancer therapy.
Inducing immunogenic cell death (ICD) of cancer cells is an important method to improve the immunogenicity of tumor for enhanced cancer immunotherapy. Therefore, we discuss the ICD process and then...
A covalent organic framework (COF)-engineered polydopamine core-shell nanoplatform (PDA@COF) was developed. The ultrasmall pores and abundant functional sites of COF rendered the nanoplatform with enhanced drug loading capacity and diminished...
Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.
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