Hemoglobin nanoclusters-mediated regulation of KPNA4 in hypoxic tumor microenvironment enhances photodynamic therapy in hepatocellular carcinoma.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Carcinoma, Hepatocellular*/drug therapy ; Liver Neoplasms*/drug therapy ; Tumor Microenvironment*/drug effects ; Photochemotherapy*/methods ; Hemoglobins*/pharmacology ; Sorafenib*/pharmacology ; Sorafenib*/therapeutic use ; Indocyanine Green*/chemistry ; Indocyanine Green*/pharmacology ; Indocyanine Green*/therapeutic use; Humans ; Animals ; Cell Line, Tumor ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; alpha Karyopherins/metabolism ; Drug Resistance, Neoplasm/drug effects ; Nanoparticles/chemistry

Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics.
Results: In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT).
Conclusion: The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.
(© 2024. The Author(s).)

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Keywords: Drug resistance; Hemoglobin nanocluster complexes; Hepatocellular carcinoma; Hypoxia; KPNA4; Mitochondrial function; Photodynamic therapy; Sorafenib

0 (Hemoglobins)
9ZOQ3TZI87 (Sorafenib)
IX6J1063HV (Indocyanine Green)
0 (Antineoplastic Agents)
0 (alpha Karyopherins)

Date Created: 20240812 Date Completed: 20240813 Latest Revision: 20240923

20240923

PMC11318167

10.1186/s12951-024-02717-9

39135024