Highly Penetrable and On-Demand Oxygen Release with Tumor Activity Composite Nanosystem for Photothermal/Photodynamic Synergetic Therapy

Abstract

A deep penetrating and pH-responsive composite nanosystem was strategically developed to improve the efficacy of synergetic photothermal/photodynamic therapy (PTT/PDT) against hypoxic tumor. The designed nanosystem ([PHC]­PP@HA NPs) was constructed by coloading hemoglobin (Hb) and chlorin e6 on polydopamine to build small-sized PHC NPs, which were encapsulated inside the polymer micelles (poly­(ethylene glycol)–poly­(ethylenimine)) and then capped with functionalized hyaluronic acid. The pH-responsive feature made [PHC]­PP@HA NPs retain an initial size of ∼140 nm in blood circulation but rapidly release small PHC NPs (∼10 nm) with a high tumor-penetrating ability in the tumor microenvironment. The in vitro penetration experiment showed that the penetration depth of PHC NPs in the multicellular tumor spheroids exceeded 110 μm. The [PHC]­PP@HA NPs exhibited excellent biocompatibility, deep tumor permeability, high photothermal conversion efficiency (47.09%), and low combination index (0.59) under hypoxic conditions. Notably, the nanosystem can freely adjust the release of oxygen and damaging PHC NPs in an on-demand manner on the basis of the feedback of tumor activity. This feedback tumor therapy significantly improved the synergistic effect of PTT/PDT and reduced its toxic side effects. The in vivo antitumor results showed that the tumor inhibition rate of [PHC]­PP@HA NPs with an on-demand oxygen supply of Hb was ∼100%, which was much better than those of PTT alone and Hb-free nanoparticles ([PC]­PP@HA NPs). Consequently, the [PHC]­PP@HA NP-mediated PTT/PDT guided by feedback tumor therapy achieved an efficient tumor ablation with an extremely low tumor recurrence rate (8.3%) 60 d later, indicating the versatile potential of PTT/PDT.

Supramolecular agents for combination of photodynamic therapy and other treatments

“…8 ). 98 The photothermal agent polydopamine, the photodynamic agent Ce6, and hemoglobin (Hb) formed supramolecular assemblies ([PHC]PP@HA NPs). The rapid oxidation that hindered Hb's functioning as an oxygen donor was prevented through supramolecular assembly with polydopamine.…”

Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials

“…The Hb in PHC NPs would continuously supply the on‐demand oxygen release to alleviate the hypoxia to enhance the PDT effect. [ 36 ]…”

Recent Advances in Functional Carbon Quantum Dots for Antitumour

“…PTT or PDT alone cannot completely eliminate tumours, so the combination of these two methods improves the curative effects. [235][236][237] Based on the upconversion luminescence (UCL) principle described above, the combination of PDT and PTT for tumour phototherapy provides a new opportunity to apply CQDs in tumour treatment. Using ZnPc as a photosensitizer and CQDs as thermal sensitizers, Lv et al prepared a nanomaterial with CQDs and UCNPs, in which the CQDs could gradually heat and ablate tumour cells while the UCNPs could transfer energy to ZnPc to generate ROS to kill the tumour cells under 980 nm near-infrared light irradiation; this method was expected to yield twice the result with half the effort.…”