Photo and Redox Dual Responsive Reversibly Cross-Linked Nanocarrier for Efficient Tumor-Targeted Drug Delivery

Shao, Yu; Shi, Changying; Xu, Gaofei; Guo, Dandan; Luo, Juntao

doi:10.1021/am501913m

Cited by 91 publications

(88 citation statements)

References 51 publications

(117 reference statements)

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“…2c–e). The critical micelle concentrations (CMCs) of the telodendrimers in PBS range from 1.14 to 2.68 µM, which was determined by a fluorescent method[49] employing Nile red as a probe (Table 1 and Fig. S15–S17).…”

Section: Resultsmentioning

confidence: 99%

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions

et al. 2016

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Novel nanocarriers are highly demanded for the delivery of heterogeneous protein therapeutics for disease treatments. Conventional nanoparticles for protein delivery are mostly based on the diffusion-limiting mechanisms, e.g., physical trapping and entanglement. We develop herein a novel linear-dendritic copolymer (named telodendrimer) nanocarrier for efficient protein delivery by affinitive coating. This affinity-controlled encapsulation strategy provides nanoformulations with a small particle size (<30 nm), superior loading capacity (>50% w/w) and maintained protein bioactivity. We integrate multivalent electrostatic and hydrophobic functionalities synergistically into the well-defined telodendrimer scaffold to fine-tune protein binding affinity and delivery properties. The ion strength and density of the charged groups as well as the structure of the hydrophobic segments are important and their combinations in telodendrimers are crucial for efficient protein encapsulation. We have conducted a series of studies to understand the mechanism and kinetic process of the protein loading and release, utilizing electrophoresis, isothermal titration calorimetry, Förster resonance energy transfer spectroscopy, bio-layer interferometry and computational methods. The optimized nanocarriers are able to deliver cell-impermeable therapeutic protein intracellularly to kill cancer cells efficiently. In vivo imaging studies revealed cargo proteins preferentially accumulate in subcutaneous tumors and retention of peptide therapeutics is improved in an orthotopic brain tumor, these properties are evidence of the improved pharmacokinetics and biodistributions of protein therapeutics delivered by telodendrimer nanoparticles. This study presents a bottom-up strategy to rationally design and fabricate versatile nanocarriers for encapsulation and delivery of proteins for numerous applications.

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Section: Resultsmentioning

confidence: 99%

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions

et al. 2016

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“…152 In this regard, disulfide bonds 153 and nitrobenzyl methyl esters 154 can be introduced into the principle chain and into copolymers to provide UV responsiveness. Shao et al 155 conjugated coumarin moieties with a polylysine moiety in a self-assembled telodendrimer polymer through disulfide bonding. Exposure to UV irradiation reversibly induced cross-linking and micelle formation without any change in drug release efficiency.…”

Section: Light Activation As a Component Of Dual/multiresponsive Smentioning

confidence: 99%

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

et al. 2017

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Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide.

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“…We have developed a series of telodendrimers with coumarin (Co) and cholic acid (CA) as peripheral groups, which self-assemble into micelles with UV sensitivity for reversible micelle crosslinking and de-crosslinking. [40] These coumarin-containing telodendrimers is expected to form pi-pi stacking with aromatic molecules, e.g. SN-38, and therefore encapsulate such kind drug efficiently within the micelles formed.…”

Section: Resultsmentioning

confidence: 99%

Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment

Shi

Guo

et al. 2015

Acta Biomaterialia

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Four coumarin-containing telodendrimers (denoted as P-I, P-II, P-III and P-IV) were designed and synthesized to self-assemble into the corresponding nanoparticles. Of those, two nanoparticles (P-II and P-IV micelles) were screened and selected for targeted drug delivery of 7-ethyl-10-hydroxy camptothecin (SN-38), a prominent and efficacious anticancer agent, for the treatment of colon cancers. The nanoparticle encapsulation significantly increased the solubility of SN-38 in aqueous solution. Dynamic light scattering (DLS) showed the size of these SN-38 nanoparticles to be around 50 nm, and rod-shaped micelles were observed using transmission electron microscopy (TEM). These two novel nanoformulations of SN-38/P-II and SN-38/P-IV were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug (SN-38 in DMSO) and were 500-fold more potent than Irinotecan (a prodrug of SN-38). In addition, near infrared fluorescent (NIRF) optical imaging was utilized to monitor the tumor targeted delivery of SN-38/NPs via co-loading a NIRF dye. It was demonstrated that these NPs preferentially accumulated in tumors when compared to healthy tissue. A pharmacokinetics study showed that SN-38 micelle formulations had a longer circulating time in blood than Irinotecan. Furthermore, SN-38 loaded nanoformulations exhibit superior anti-tumor efficacy when compared with Irinotecan at equivalent SN-38 dose in HT-29 human colon cancer xenograft models.

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Photo and Redox Dual Responsive Reversibly Cross-Linked Nanocarrier for Efficient Tumor-Targeted Drug Delivery

Cited by 91 publications

References 51 publications

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment

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