Self-delivery photothermal converter for feedback enhanced tumor therapy by cascade inflammation inhibition

Abstract

Photothermal therapy (PTT) for tumor could induce cascade inflammation responses, which in turn promote tumorigenesis, invasion and metastasis. In this paper, a self-delivery photothermal converter (designated as CypCel) is fabricated for feedback enhanced tumor therapy based on hydrophobic and electrostatic interactions between photothermal agent Cypate (Cyp) and anti-inflammatory drug Celecoxib (Cel). Carrier free CypCel holds extremely high drug contents as well as favorable stability and photothermal property. Upon laser irradiation, CypCel induces local hyperpyrexia to restrain tumor proliferation by Cyp-mediated PTT. More importantly, the light-triggered degradation of CypCel causes fast release of Cel for cascade inflammation inhibition, which reverses the pro-inflammatory microenvironment caused by PTT. After intravenous injection, nanosized CypCel prefers to accumulate into tumor site through enhanced permeability and retention (EPR) effect, and subsequently penetrates into tumor tissue for effective cellular uptake. Ultimately, the photothermal converter with anti-inflammatory property significantly suppresses tumor growth with negligible systemic toxicity. This study would advance the development of carrier-free nanomedicine against malignancies and inflammation-associated diseases.