Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy

  • Adv Sci (Weinh). 2024 Mar 14:e2306684. doi: 10.1002/advs.202306684.
Anara Molkenova  1 ,  Hye Eun Choi  1 ,  Gibum Lee  2 ,  Hayeon Baek  3 ,  Mina Kwon  1 ,  Su Bin Lee  1 ,  Jeong-Min Park  4 ,  Jae-Hyuk Kim  4 ,  Dong-Wook Han  5 ,  Jungwon Park  3 ,  Sei Kwang Hahn  2 ,  Ki Su Kim  1
Affiliations
  • 1. School of Chemical Engineering, Department of Organic Materials Science and Engineering, Institute for Advanced Organic Materials, Pusan National University, Busan, 46241, Republic of Korea.
  • 2. Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
  • 3. School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
  • 4. Department of Civil and Environmental Engineering, Pusan National University, Busan, 46241, Republic of Korea.
  • 5. Department of Cogno-Mechatronics Engineering, BIO-IT Fusion Technology Research Institute, Pusan National University, Busan, 46241, Republic of Korea.
PMID: 38482992 DOI: 10.1002/advs.202306684
Abstract

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2 -Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin Cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2 -Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2 -Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in Cancer therapy.

Keywords
cryotherapy; hyaluronate; photodynamic therapy; synergistic cancer therapy; upconversion nanoparticles.
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