RESUMO
A new strategy for the detection of hypoxia and NO succeeded by photocontrolled delivery of an anticancer agent has been demonstrated. The developed system is able to produce distinct responses (dual channel) upon interaction with hypoxia and NO. This probe can also release anticancer drugs upon photoirradiation acting potentially as both a dual-analyte imaging agent and a prodrug.
RESUMO
'Aggregation Induced Emission + Excited State Intramolecular Proton Transfer (AIE + ESIPT)'-assisted photorelease of an anticancer drug by a p-hydroxyphenacyl (pHP) phototrigger with real-time monitoring has been demonstrated.
Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/química , Nanopartículas/química , Fenilacetatos/química , Prótons , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Fenilacetatos/farmacologia , Processos Fotoquímicos , Fatores de TempoRESUMO
Remedial cancer therapy deals with a large number of theranostic applications. However, systems, so far known, are only capable of single surveillance for both diagnostic and therapeutic modes of action. A nanosystem, which can be localized to the cancer and deliver the chemotherapeutic agent on demand, will provide effective therapeutic activity. Herein, we designed a single component nanoprodrug ANPD-X (Activatable Nano Pro-Drug-X) which indentified the tumor sites by fluorescent color change (signal 1, blue to green fluorescence) using H2O2-mediated oxidation of boronate fluorophore. In the next step, precise spatiotemporal irradiation of light only on identified tumor sites resulted in the release of anticancer drug chlorambucil. The real time information on drug release was achieved by a second fluorescence color change (signal 2, green to blue fluorescence). Thus, nanoprodrug ANPD-X provided overall two-step surveillance in the anticancer drug delivery. Activation of the ANPD-X after addition of H2O2 and drug release upon photoirradiation was investigated in vitro by monitoring its fluorescence in the HeLa cell line.
Assuntos
Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Células HeLa , Humanos , Peróxido de Hidrogênio , Pró-FármacosRESUMO
In spite of inventing several anticancer agents the clinical payoff still remains unsatisfactory because of their severe host toxicity due to their nonspecific biodistribution in the body. To achieve high efficiency in anti-cancer drug delivery, thus, we designed and developed a single component photoresponsive drug delivery system, a fusion of two platforms spiropyran and coumarin, which synchronizes two controlling factors: first, the lower pH of cancer tissue, which acts as an internal control and leads to the ring opening of spiropyran resulting in a distinct colour change and fluorescence activation of coumarin; and second, the release of the anti-tumor drug by the externally controlled light. Highly fluorescent nature and promising biocompatibility make the SP-Cou-Cbl system suitable for cell imaging and in vitro studies.
RESUMO
Correction for 'A spiropyran-coumarin platform: an environment sensitive photoresponsive drug delivery system for efficient cancer therapy' by Shrabani Barman et al., J. Mater. Chem. B, 2017, DOI: 10.1039/c7tb00379j.
RESUMO
Among the well-known phototriggers, the p-hydroxyphenacyl (pHP) group has consistently enabled the very fast, efficient, and high-conversion release of active molecules. Despite this unique behavior, the pHP group has been ignored as a delivery agent, particularly in the area of theranostics, because of two major limitations: Its excitation wavelength is below 400â nm, and it is nonfluorescent. We have overcome these limitations by incorporating a 2-(2'-hydroxyphenyl)benzothiazole (HBT) appendage capable of rapid excited-state intramolecular proton transfer (ESIPT). The ESIPT effect also provided two unique advantages: It assisted the deprotonation of the pHP group for faster release, and it was accompanied by a distinct fluorescence color change upon photorelease. Inâ vitro studies showed that the p-hydroxyphenacyl-benzothiazole-chlorambucil conjugate presents excellent properties, such as real-time monitoring, photoregulated drug delivery, and biocompatibility.
Assuntos
Antineoplásicos Alquilantes/química , Benzotiazóis/química , Clorambucila/química , Sistemas de Liberação de Medicamentos , Antineoplásicos Alquilantes/administração & dosagem , Linhagem Celular Tumoral , Clorambucila/administração & dosagem , Humanos , Microscopia Confocal , PrótonsRESUMO
Nanocarrier-mediated photodynamic therapy (PDT) is an effective tool for anti-tumour treatment due to the targeted and image-guided delivery of photosensitizers (PSs) to diseased tissues. These nanocarriers range from inorganic, ceramic, polymeric to biological nanoparticles (NPs). Such PS-grafted bicomponent nanocarriers have limitations like (i) difficulty in surface modification, (ii) lower loading percentages of the therapeutic agent, (iii) unstable physical encapsulation, etc. By any means, if we can prepare PSs directly as NPs then we can surpass the above drawbacks. Hence, we synthesised new two-photon fluorene-functionalised morpholine (Fluo-Mor)-based organic NPs that showed strong fluorescence and profound photodynamic therapy (PDT) activity only in acidic medium. Such a pH-responsive appearance of fluorescence enables Fluo-Mor NPs for the real time monitoring of photodynamic therapeutic activity selectively in low-pH organelles viz. lysosome. Cytotoxicity of Fluo-Mor NPs was monitored using time-dependent and dose-dependent cancer cell viability assay and confocal imaging.
RESUMO
We have developed an ESIPT based drug delivery system (DDS), Cou-Benz-Cbl conjugate, by incorporating a benzothiazole group at the 8th position of the 7-hydroxy-coumarin moiety for pH sensitive fluorescence properties and photocontrolled release of the anticancer drug chlorambucil. The Cou-Benz-Cbl conjugate exhibited unique photophysical properties like good absorbance at around 350 nm, a large Stokes shift (â¼151 nm) and pH sensitive fluorescence properties. The pH sensitive fluorescence properties of the Cou-Benz-Cbl conjugate can be ascribed to an ESIPT turn "on and off" mechanism. At physiological pH, the ESIPT gets turned "off" and a blue fluorescence of the coumarin moiety was observed, but at acidic pH, the ESIPT gets turned "on" and a green fluorescence was noted. Photolysis of the Cou-Benz-Cbl conjugate using UV light of wavelength ≥365 nm resulted in the efficient release of the anticancer drug chlorambucil. Cellular uptake studies revealed that the Cou-Benz-Cbl conjugate was easily internalized inside the cancer cells. Further, an MTT assay showed that the Cou-Benz-Cbl conjugate has a good biocompatibility and low cytotoxicity towards the MDA-MB-231 cell line, whereas upon exposure to UV light, the Cou-Benz-Cbl conjugate exhibited enhanced cytotoxicity compared to the free drug due to the effective release of the anticancer drug chlorambucil inside the cancer cell.