Dataset Information

One-photon red light-triggered disassembly of small-molecule nanoparticles for drug delivery

ABSTRACT:

Background

Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states.

Results

Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo.

Conclusions

This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s12951-021-01103-z.

SUBMITTER: Long K

PROVIDER: S-EPMC8567723 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:One of the challenges in designing a successful drug-delivery vehicle is the control over drug release. Toward this, a number of multifunctional nanoparticles with multiple triggers and complex chemistries have been developed. To achieve an efficient and maximum therapeutic effect, a trigger dependent drug-delivery system with sustained release is desirable. In this paper, we report the use of a combination of thermoresponsive gold core and polymeric shell nanoparticles that can provide a sustained, triggered release of doxorubicin, making the system more efficient compared to individual nanoparticles. The selection of the system was dependent on the best trigger applicable in biological systems and a component responsive to that trigger. Because of the best tissue penetration depth observed for radiofrequency (rf), we chose rf as a trigger. Whereas the gold nanoparticles (AuNPs) provided hyperthermia trigger on exposure to rf fields, the thermoresponsiveness was endowed by poly(N-isopropylacrylamide) (pNIPAm)-based polymer shells. AuNPs with three different compositions of shells, only pNIPAm and p(NIPAm-co-NIPMAm) with the ratio of NIPAm/N-(isopropylmethacrylamide) (NIPMAm) 1:1 (pNIPMAm50) and 1:3 (pNIPMAm75), were synthesized. We observed that the polymer coating on the AuNPs did not affect the heating efficiency of AuNPs by rf and exhibited a temperature-dependent release of the chemotherapeutic drug, doxorubicin. The nanoparticles were biocompatible, stable in biologically relevant media, and were able to show a burst as well as a sustained release, which was rf-dependent. Interestingly, we observed that when HeLa cells were treated with doxorubicin-loaded gold core-polymeric shell NPs and exposed to rf for varying times, the mixture of the two polymeric shell nanoparticles induced more cell death as compared to the cells treated with single nanoparticles, suggesting that such multi-nanoparticle systems can be more efficacious delivery systems instead of a single multicomponent system.