Protein-Activatable Diarylethene Monomer as a Smart Trigger of Noninvasive Control Over Reversible Generation of Singlet Oxygen: A Facile, Switchable, Theranostic Strategy for Photodynamic-Immunotherapy

Abstract

The development of activatable photosensitizers to allow for the reversible control of singlet oxygen (1O2) production for photodynamic therapy (PDT) faces great challenges. Fortunately, the flourishing field of supramolecular biotechnology provides more effective strategies for activatable PDT systems. Here, we developed a new reversible PDT on a switch that controls the 1O2 generation of self-assembled albumin nanotheranostics in vitro and in vivo. A new molecular design principle of aggregation-induced self-quenching photochromism and albumin on-photoswitching was demonstrated using a new asymmetric, synthetic diarylethene moiety DIA. The photosensitizer porphyrin and DIA were incorporated as building blocks in a glutaraldehyde-induced covalent albumin cross-linking nanoplatform, HSA–DIA–porphyrin nanoparticles (NPs). More importantly, the excellent photoswitching property of DIA enables the resultant nanoplatform to act as a facile, switchable strategy for photodynamic-immunotherapy.

Photodynamic Therapy—Current Limitations and Novel Approaches

“…A 1:2 demultiplexer based on a Zn 2+ -terpyridine-Bodipy conjugate was reported to remain in an “ON” state, unless 1 O 2 generated by photosensitization triggered apoptotic response, which resulted in autonomous switching “OFF” of 1 O 2 generation ( Turan et al, 2018 ). Another approach, which allows for a switchable strategy for photodynamic-immunotherapy, takes advantage of a switch that controls the 1 O 2 generation of self-assembled albumin nanotheranostics ( Cheng et al, 2021 ). In another study, Yoon et al reported a nanomaterial which self-assembles from phthalocyanine building blocks.…”

Self-assembled nanoparticles based on supramolecular-organic frameworks and temoporfin for an enhanced photodynamic therapy in vitro and in vivo

“…40 Three types of water-soluble 3D SOFs (SOFs 1-3) were used to construct self-assembled nanoparticles. These SOFs were co-assembled with tetracationic monomers T4-6 and cucurbit [8]uril (CB [8]). Monomers T4-6 share a similar (4-phenyl)pyridinium building block with different positive or neutral terminal groups.…”

“…The construction procedure of SOFs is consistent with previously reported studies. [35][36][37][38][39] Generally, T4-6 were first dissolved in deionized water ([T4-6] = 1 mM) and CB [8] powder was added into the solution. The mixture was heated and then cooled to room temperature to form SOFs 1-3. mTHPC-SOFs 1-3 were constructed by the addition of mTHPC DMSO solution into SOF aqueous solution slowly and dialyzed against deionized water.…”

“…The PS is activated, and the excited PS transfers its energy to molecular oxygen to generate highly cytotoxic reactive oxygen species (ROSs), such as singlet oxygen ( 1 O 2 ). [1][2][3][4][5][6][7][8][9][10] Therefore, PDT could highly efficiently kill cancer cells in a localized fashion to minimize the side effects toward normal tissues.…”

Recent near-infrared light-activated nanomedicine toward precision cancer therapy

“…148 As for photoisomerization, spiropyran and its derivatives are typical examples to be used in a controllable strategy. 149 They can become hydrophilic from hydrophobic under high-energy light irradiation owing to the formation of a ring-opening structure, which was grafted onto mesoporous silica-coated UCNPs (UCNP@mSiO 2 ) to control drug access. 150 Specifically, in the hydrophobic spiropyran layer, hydrophobic drugs could be sealed in the pores of silica, whereas the hydrophilic spiropyran layer caused by local UV light from UCNPs upon NIR irradiation would lead to the release of the drug for therapy.…”