Self assembled dual responsive micelles stabilized with protein for co-delivery of drug and siRNA in cancer therapy

Alex, M.R. Aji; Nehate, Chetan; Veeranarayanan, Srivani; Kumar, D. Sakthi; Kulshreshtha, Ritu; Koul, Veena

doi:10.1016/j.biomaterials.2017.04.022

Cited by 78 publications

(24 citation statements)

References 31 publications

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“…27,52 Although it has been shown that these NPs bind with serum protein (bovine serum albumin (BSA)) readily, greater stability and longer circulation times were observed in vivo . 39,62 Results herein showed homogeneous spherical structures of NPs after systemic injection (Figure 1C) using TEM, indicating that the stability of NP was retained in systemic circulation.…”

Section: Resultsmentioning

confidence: 56%

“…In fact, this pH-responsive behavior is not unique to the GSK-3 β inhibitor, since it has been shown in previous studies that release of doxorubicin, which also has amines, was pH dependent. 37,39 Nile red, which has no protonatable groups, did not show any pH-dependent change in release. 37,39 Co-localization of NPs and lysosomes was observed, together with enhanced drug efficacy when delivered with NPs, and indicates that a sustained intracellular release of drug from lysosomes via the NP delivery system likely occurs, as lipophilic small molecules that are <700 Da molecular weight are freely permeable across the cell membrane.…”

Section: Resultsmentioning

confidence: 84%

“…37,39 Nile red, which has no protonatable groups, did not show any pH-dependent change in release. 37,39 Co-localization of NPs and lysosomes was observed, together with enhanced drug efficacy when delivered with NPs, and indicates that a sustained intracellular release of drug from lysosomes via the NP delivery system likely occurs, as lipophilic small molecules that are <700 Da molecular weight are freely permeable across the cell membrane. 79 This pH-responsive release is beneficial for the design of NPs since it provides a maximum release of drug at endosomal pH, reducing the possibility of premature drug release during systemic circulation.…”

Section: Resultsmentioning

confidence: 84%

“…PSMA- b -PS-based NPs, which have shown excellent loading and sustained release of multiple hydrophobic drugs, 36–39 offer vast chemical versatility for functionalization with various targeting ligands for tissue/cell-specific affinity due to myriad maleic anhydride carboxylic acid groups. 38,40,41 To enhance drug accumulation at sites of bone remodeling, a peptide with high affinity for tartrate-resistant acid phosphate (TRAP), 42 a protein deposited on bone resorptive surfaces, was introduced to NPs.…”

mentioning

confidence: 99%

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Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing

et al. 2017

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Despite several decades of progress, bone-specific drug delivery is still a major challenge. Current bone-acting drugs require high-dose systemic administration which decreases therapeutic efficacy and increases off-target tissue effects. Here, a bone-targeted nanoparticle (NP) delivery system for a β-catenin agonist, 3-amino-6-(4-((4-methylpiperazin-1-yl)-sulfonyl)phenyl)-N-(pyridin-3-yl)pyrazine-2-carboxamide, a glycogen synthase kinase 3 beta (GSK-3β) inhibitor, was developed to enhance fracture healing. The GSK-3β inhibitor loading capacity was found to be 15 wt % within highly stable poly(styrene-alt-maleic anhydride)-b-poly(styrene) NPs, resulting in ~50 nm particles with ~ −30 mV surface charge. A peptide with high affinity for tartrate-resistant acid phosphatase (TRAP), a protein deposited by osteoclasts on bone resorptive surfaces, was introduced to the NP corona to achieve preferential delivery to fractured bone. Targeted NPs showed improved pharmacokinetic profiles with greater accumulation at fractured bone, accompanied by significant uptake in regenerative cell types (mesenchymal stem cells (MSCs) and osteoblasts). MSCs treated with drug-loaded NPs in vitro exhibited 2-fold greater β-catenin signaling than free drug that was sustained for 5 days. To verify similar activity in vivo, TOPGAL reporter mice bearing fractures were treated with targeted GSK-3β inhibitor-loaded NPs. Robust β-galactosidase activity was observed in fracture callus and periosteum treated with targeted carriers versus controls, indicating potent β-catenin activation during the healing process. Enhanced bone formation and microarchitecture were observed in mice treated with GSK-3β inhibitor delivered via TRAP-binding peptide-targeted NPs. Specifically, increased bone bridging, ~4-fold greater torsional rigidity, and greater volumes of newly deposited bone were observed 28 days after treatment, indicating expedited fracture healing.

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Section: Resultsmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 84%

mentioning

confidence: 99%

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Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing

et al. 2017

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“…There are many drug-excipient interaction studies reported for conventional dosage forms such as tablets and capsules [3]. But nowadays a good number of reports are there on bovine serum albumin (BSA) and doxorubicin hydrochloride (Dox) for tumor targeted delivery [4][5][6][7]. In this scenario, it would be interesting to carry out a study on interactions between Dox and BSA.…”

Section: Introductionmentioning

confidence: 99%

A Preformulation Study on Interactions Between Doxorubicin Hydrochloride and Bovine Serum Albumin

Ajithkumar

Pramod

2017

Int J App Pharm

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Objective: The objective was to study the effect of concentrations of doxorubicin hydrochloride (Dox) and bovine serum albumin (BSA) in a sample on fluorescence intensity, UV absorbance, refractive index and optical rotation. Methods:A circumscribed central composite statistical design with 2 factors, 5 levels, and 13 runs was selected for the study. According to that influence of both in interaction was measured by fluorescence intensity, UV absorbance, refractive index and optical rotation and were analyzed by the design expert software. Results:It was observed that concentration of BSA alone was significantly affecting the fluorescence intensity and optical rotation of samples. Dox alone was having a significant effect on UV absorbance at 280 nm. In the case of a refractive index, both Dox and BSA were having a significant effect. But the effect of BSA was much pronounced than that of Dox on refractive index. Conclusion:Interaction studies between BSA and Dox would be beneficial as they are commonly used in combination with tumor-targeted delivery. The interaction was observed that in a linear model for a wide range of concentration of both. So it will be useful to determine the interaction of unknown concentration.

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Stimuli‐Responsive Nanotechnology for RNA Delivery

Zhou,

Chen,

et al. 2023

Advanced Science

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Ribonucleic acid (RNA) drugs have shown promising therapeutic effects for various diseases in clinical and preclinical studies, owing to their capability to regulate the expression of genes of interest or control protein synthesis. Different strategies, such as chemical modification, ligand conjugation, and nanotechnology, have contributed to the successful clinical translation of RNA medicine, including small interfering RNA (siRNA) for gene silencing and messenger RNA (mRNA) for vaccine development. Among these, nanotechnology can protect RNAs from enzymatic degradation, increase cellular uptake and cytosolic transportation, prolong systemic circulation, and improve tissue/cell targeting. Here, a focused overview of stimuli‐responsive nanotechnologies for RNA delivery, which have shown unique benefits in promoting RNA bioactivity and cell/organ selectivity, is provided. Many tissue/cell‐specific microenvironmental features, such as pH, enzyme, hypoxia, and redox, are utilized in designing internal stimuli‐responsive RNA nanoparticles (NPs). In addition, external stimuli, such as light, magnetic field, and ultrasound, have also been used for controlling RNA release and transportation. This review summarizes a wide range of stimuli‐responsive NP systems for RNA delivery, which may facilitate the development of next‐generation RNA medicines.

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Self assembled dual responsive micelles stabilized with protein for co-delivery of drug and siRNA in cancer therapy

Cited by 78 publications

References 31 publications

Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing

Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing

A Preformulation Study on Interactions Between Doxorubicin Hydrochloride and Bovine Serum Albumin

Stimuli‐Responsive Nanotechnology for RNA Delivery

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