10.1002/9781118797914

Vollständiger Abstract

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Conventional platinum(II)-based therapeutics suffer from poor pharmacokinetics, often leading to severe systemic toxicity and compromised therapeutic outcomes. Here, we present a supramolecular engineering approach for precise drug delivery and real-time monitoring of platinum(II) agents during therapy. Specifically, near-infrared (NIR)-emissive platinum(II) complex-based polymeric nanomicelles were fabricated via electrostatic assembly, which enable sustained release of cytotoxic platinum(II) agents at tumor sites with deep tumor penetration. Crucially, the released platinum(II) monomer exhibits bright green phosphorescence upon binding to DNA. This generates a complementary dual-emissive system: NIR emission from the platinum(II) oligomers allows in vivo imaging of biodistribution, while visible green emission from DNA-bound monomers enables real-time monitoring of drug-target interaction dynamics. Photophysical mechanistic studies reveal that monomeric platinum(II) complexes undergo fast nonradiative decay governed by intramolecular vibronic wavefunction overlap. For oligomeric species, extended intermetallic interactions weaken exciton-vibration coupling and correspondingly reduce vibronic overlap between electronic states, thereby suppressing nonradiative dissipation and enhancing luminescence efficiency. The nanomicelles exhibit remarkable tumor-targeting selectivity and prolonged retention in tumor tissues, achieving significant tumor regression in vivo through synergistic chemo-photodynamic therapy, with a 92.2% reduction in tumor volume. This supramolecular strategy overcomes key challenges in platinum-based therapeutics and provides an integrated paradigm with strong potential for precision oncology.

Abstract: PubMed · Datensatz