RESUMO
Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.
Assuntos
Carbono , Imunoterapia , Rodaminas , Animais , Camundongos , Rodaminas/química , Carbono/química , Fototerapia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Corantes Fluorescentes/químicaRESUMO
The reversible phase transfer of compounds between two immiscible liquid phases has many applications in a wide range of fields, and ionic liquids have been widely used as potential functional solvents and catalysts. However, photo-triggered reversible phase transfer of ionic liquids between the organic phase and water phase has not been reported so far. In the present work, the reversible phase transfer of six kinds of azobenzene-based ionic liquid surfactants between the organic phase and water phase is investigated by alternative irradiation of UV and visible light. Factors affecting the transfer efficiency, such as chemical structure and concentration of the ionic liquid surfactants, equilibrium photo-isomerization degree, and the aggregation state of ionic liquid surfactants are investigated in detail. It is shown that transfer efficiency greater than 89% was achieved under optimal conditions, equilibrium photo-isomerization degree of the ionic liquid surfactants is the main factor to determine their transfer efficiencies, and the aggregation of cis-isomers is not beneficial for the transfer.
Assuntos
Compostos Azo/química , Líquidos Iônicos/química , Óleos/química , Tensoativos/química , Água/químicaRESUMO
In this study we constructed spherical photo-responsive microcapsules composed of three photo-switchable DNA strands. These strands first formed a three-way junction (TWJ) motif that further self-assembled to form microspheres through hybridization of the sticky-end regions of each branch. To serve as the photo-switch, multiple unmodified azobenzene (Azo) or 2,6-dimethyl-4-(methylthio)azobenzene (SDM-Azo) were introduced into the sticky-end regions via a d-threoninol linker. The DNA capsule structure deformed upon trans-to-cis isomerization of Azo or SDM-Azo induced by specific light irradiation. In addition, photo-triggered release of encapsulated small molecules from the DNA microcapsule was successfully achieved. Moreover, we demonstrated that photo-triggered release of doxorubicin caused cytotoxicity to cultured cells. This biocompatible photo-responsive microcapsule has potential application as a photo-controlled drug-release system.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Compostos Azo/química , DNA/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Luz , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Cápsulas/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/síntese química , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Células HEK293 , Humanos , Processos FotoquímicosRESUMO
Tumor-oriented nanocarrier drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. Here we described a nanostructured lipid carrier (NLC) modified with photo-responsive cell-penetrating peptides (pCPP-NLC). The conventional cell penetrating peptide (CPP)-mediated intracellular drug delivery system sometimes seemed limited due to the lack of target selectivity of the cell penetrating activity. In this study, pCPP (CKRRMK(Nvoc)WK(Nvo0c)K(Nvoc)), a photo-responsive CPP originated from the CPP (CKRRMKWKK), was endowed photo-responsiveness after masking of lysines in the sequence of CPP with photolabile-protective groups, and was introduced onto the surface of NLC. Accordingly, upon reaching the tumor tissues, pCPP-NLC enhance specific cancer cellular uptake after rapidly cleaving the photolabile-protective group, in this case, illumination in the presence of UV-light. In contrast, in circulation, the penetration was shielded. The pCPP-NLC carrying paclitaxel (PTX) prepared in this work possessed suitable physiochemical properties such as small particle size, high drug encapsulation efficiency, and good stability. The strong cellular uptake and cytotoxic activity of pCPP-NLC in HT-1080 cells verified the correlation with illumination. The remarkable penetration into HT-1080 multicellular tumor spheroids confirmed that the temporary mask of the photolabile-protective group in pCPP does not disturb the penetration ability of CPP in the tumor microenvironment with illumination. Furthermore, the triggered activation exhibited higher antitumor efficacy with the tumor spheroids compared with the non-modified NLC (N-NLC) and Taxol(®). In conclusion, the application of pCPP modifications may be an approach for the selectively targeted delivery of anti-tumor agents.