A dynamic protein corona substitution strategy for activatable imaging-guided synergistic theranostics in...

Area of Science:

• Nanomedicine
• Oncology
• Bioconjugate Chemistry

Background:

• Antibody-drug conjugates (ADCs) show limitations in triple-negative breast cancer (TNBC) therapy due to protein corona effects and drug resistance.
• Existing nanocarriers often face targeting inefficiency and premature drug release, hindering therapeutic outcomes.

Purpose of the Study:

• To develop a dynamic protein corona substitution (PCS) strategy to overcome ADC limitations in TNBC.
• To engineer a nanoplatform for tumor microenvironment-responsive drug delivery, enhanced targeting, and combination therapy.

Main Methods:

• Self-assembly of disulfide-bridged camptothecin (CPT) and Cy-OH into nanoparticles (NPs).
• Utilizing glutathione (GSH) for triggered drug release and albumin recruitment, forming albumin-cloaked NPs.
• Employing near-infrared (NIR)-I&II fluorescence for tumor monitoring and albumin-mediated transcytosis for enhanced penetration.

Main Results:

• The PCS strategy successfully remodeled the nanoparticle protein corona, enhancing tumor penetration and drug retention.
• Albumin-cloaked NPs demonstrated real-time tumor monitoring and reversed CPT resistance.
• Combination therapy with photothermal-photodynamic therapy (PTT/PDT) showed amplified antitumor effects in TNBC models.

Conclusions:

• The developed nanoplatform offers a paradigm for protein corona reprogramming in precision oncology.
• This approach enhances specificity and synergistic antitumor effects for TNBC treatment.
• Dynamic protein corona substitution presents a promising strategy to improve nanomedicine efficacy.