scholarly journals Near-Infrared Light-Responsive Shell-Crosslinked Micelles of Poly(d,l-lactide)-b-poly((furfuryl methacrylate)-co-(N-acryloylmorpholine)) Prepared by Diels–Alder Reaction for the Triggered Release of Doxorubicin

Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7913
Author(s):  
Sonyabapu Yadav ◽  
Kalyan Ramesh ◽  
Parveen Kumar ◽  
Sung-Han Jo ◽  
Seong II Yoo ◽  
...  

In the present study, we developed near-infrared (NIR)-responsive shell-crosslinked (SCL) micelles using the Diels–Alder (DA) click reaction between an amphiphilic copolymer poly(d,l-lactide)20-b-poly((furfuryl methacrylate)10-co-(N-acryloylmorpholine)78) (PLA20-b-P(FMA10-co-NAM78)) and a diselenide-containing crosslinker, bis(maleimidoethyl) 3,3′-diselanediyldipropionoate (BMEDSeDP). The PLA20-b-P(FMA10-co-NAM78) copolymer was synthesized by RAFT polymerization of FMA and NAM using a PLA20-macro-chain transfer agent (PLA20-CTA). The DA reaction between BMEDSeDP and the furfuryl moieties in the copolymeric micelles in water resulted in the formation of SCL micelles. The SCL micelles were analyzed by 1H-NMR, FE-SEM, and DLS. An anticancer drug, doxorubicin (DOX), and an NIR sensitizer, indocyanine green (ICG), were effectively incorporated into the SCL micelles during the crosslinking reaction. The DOX/ICG-loaded SCL micelles showed pH- and NIR-responsive drug release, where burst release was observed under NIR laser irradiation. The in vitro cytotoxicity analysis demonstrated that the SCL was not cytotoxic against normal HFF-1 cells, while DOX/ICG-loaded SCL micelles exhibited significant antitumor activity toward HeLa cells. Thus, the SCL micelles of PLA20-b-P(FMA10-co-NAM78) can be used as a potential delivery vehicle for the controlled drug release in cancer therapy.

2018 ◽  
Vol 9 (39) ◽  
pp. 4813-4823 ◽  
Author(s):  
Sabrina Aufar Salma ◽  
Maheshkumar Prakash Patil ◽  
Dong Woo Kim ◽  
Cuong Minh Quoc Le ◽  
Byung-Hyun Ahn ◽  
...  

We report a facile and efficient preparation of a NIR-triggered micelle system for a drug vehicle.


2015 ◽  
Vol 112 (7) ◽  
pp. 1953-1958 ◽  
Author(s):  
Ryan S. Stowers ◽  
Shane C. Allen ◽  
Laura J. Suggs

Hydrogels are widely used as in vitro culture models to mimic 3D cellular microenvironments. The stiffness of the extracellular matrix is known to influence cell phenotype, inspiring work toward unraveling the role of stiffness on cell behavior using hydrogels. However, in many biological processes such as embryonic development, wound healing, and tumorigenesis, the microenvironment is highly dynamic, leading to changes in matrix stiffness over a broad range of timescales. To recapitulate dynamic microenvironments, a hydrogel with temporally tunable stiffness is needed. Here, we present a system in which alginate gel stiffness can be temporally modulated by light-triggered release of calcium or a chelator from liposomes. Others have shown softening via photodegradation or stiffening via secondary cross-linking; however, our system is capable of both dynamic stiffening and softening. Dynamic modulation of stiffness can be induced at least 14 d after gelation and can be spatially controlled to produce gradients and patterns. We use this system to investigate the regulation of fibroblast morphology by stiffness in both nondegradable gels and gels with degradable elements. Interestingly, stiffening inhibits fibroblast spreading through either mesenchymal or amoeboid migration modes. We demonstrate this technology can be translated in vivo by using deeply penetrating near-infrared light for transdermal stiffness modulation, enabling external control of gel stiffness. Temporal modulation of hydrogel stiffness is a powerful tool that will enable investigation of the role that dynamic microenvironments play in biological processes both in vitro and in well-controlled in vivo experiments.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Jianbo Zhao ◽  
Xingxing Liang ◽  
Hui Cao ◽  
Tianwei Tan

AbstractPhoto-controlled release hydrogel provides a new strategy for treating tumours. Under the stimulation of external light sources, the ability to release the entrapped drug on time and space on demand has outstanding advantages in improving drug utilisation, optimising treatment, and reducing toxicity and side effects. In this study, a photo-controlled drug delivery system for disulphide cross-linked polyaspartic acid (PASP-SS) hydrogels encapsulating proteinase K (ProK) adsorbed with platinum nanoparticles (PtNPs) was designed. The injectable cysteamine-modified polyaspartic acid (PASP-SH) sol and PtNPs adsorbed by ProK (ProK-PtNPs) as regulatory factors were prepared. Then, ProK-PtNPs and lentinan were dissolved in the sol, and the oxidant was added to the matrix to form the gel in situ quickly after injection. Finally, the degradation of PASP-SS hydrogel by ProK and the controllability of drug release under near-infrared (NIR) light irradiation were elucidated. In vitro degradation of hydrogels and drug release experiments showed that the degradation rate of PASP-SS hydrogel significantly increased and the drug release rate increased significantly under near-infrared radiation. The results of cytotoxicity test showed that PASP-SS, ProK-PtNPs, and lentinan all had more than 90% cell survival rate on NIH3T3, and the lentinan released from the carrier obviously inhibited the proliferation of MCF7. PASP hydrogel has the potential to respond to on-demand light control.


2020 ◽  
Vol 16 (9) ◽  
pp. 1381-1393
Author(s):  
Yuan Peng ◽  
Zhenwei Su ◽  
Xin Wang ◽  
Teng Wu ◽  
Hong Xiao ◽  
...  

Chemotherapy of hepatocellular carcinoma (HCC) is facing drug resistance, which leads to unsatisfactory therapeutic effect. Thus, a combination therapy using multiple drugs may overcome this challenge. The current study aims to realize a synergistic chemotherapy of HCC by using a near-infrared light (NIR) responsive nanocarrier to co-deliver the chemotherapeutic drug Doxorubicin (DOX) and molecular targeting agent Sorafenib (SF). The nanocarrier, which could effectively load DOX in its aqueous core while SF and IR-780 in its lipid bilayer, is fabricated from a temperature-sensitive liposome (TSL) modified with PF127. An efficient SF and DOX co-loading was achieved, and meanwhile the effective photothermal conversion of IR-780 under NIR laser may cause a disassembly of the liposome structure which may trigger a rapid drug release in tumor site, greatly boosting the synergetic chemotherapeutic effect. The NIR laser-triggered drug release and the synergistic anti-tumor effect were evaluated both in cell and animal experiments, which revealed that the PF127-modified TSL is a potent nanoplatform to improve the HCC treatment through co-delivering a drug combination.


2015 ◽  
Vol 51 (32) ◽  
pp. 6948-6951 ◽  
Author(s):  
Yanfeng Zhang ◽  
Qian Yin ◽  
Jonathan Yen ◽  
Joanne Li ◽  
Hanze Ying ◽  
...  

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.


2013 ◽  
Vol 26 (15) ◽  
pp. 2424-2430 ◽  
Author(s):  
Li Zhou ◽  
Zhaowei Chen ◽  
Kai Dong ◽  
Meili Yin ◽  
Jinsong Ren ◽  
...  

2017 ◽  
Vol 61 ◽  
pp. 54-65 ◽  
Author(s):  
Francisco Martín-Saavedra ◽  
Eduardo Ruiz-Hernández ◽  
Clara Escudero-Duch ◽  
Martín Prieto ◽  
Manuel Arruebo ◽  
...  

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Matthew R. DeWitt ◽  
Allison M. Pekkanen ◽  
John Robertson ◽  
Christopher G. Rylander ◽  
Marissa Nichole Rylander

Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41–43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.


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