Modulating the tumoral SPARC content to enhance albumin-based drug delivery for cancer therapy.
J Control Release
; 366: 596-610, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38184232
ABSTRACT
Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich in cysteine (SPARC) has high binding affinity to albumin and has been shown to enhance the penetration and uptake of albumin-based drug carriers in tumors. Here, we developed a strategy to alter the tumor microenvironment (TME) by upregulating SPARC to enhance the delivery efficiency of albumin-based drug carriers into tumors. We prepared albumin nanoparticles encapsulating an NF-κB controllable CRISPR activation system (SP-NPs). SP-NPs achieved tumor-selective SPARC upregulation by responding to the highly activated NF-κB in tumor cells. Whereas a single dose of SP-NPs only modestly upregulated SPARC expression, serial administration of SP-NPs created a positive feedback loop that induced progressive increases in SPARC expression as well as tumor cell uptake and tumor penetration of the nanoparticles in vitro, in organoids, and in subcutaneous tumors in vivo. Additionally, pre-treatment with SP-NPs significantly enhanced the anti-tumor efficacy of Abraxane, a commercialized albumin-bound paclitaxel nanoformulation. Our data provide evidence that modulating SPARC in the TME can enhance the efficiency of albumin-based drug delivery to solid tumors, which may result in new strategies to increase the efficacy of nanoparticle-based cancer drugs.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Neoplasias
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article