Emergence of Gold‐Mesoporous Silica Hybrid Nanotheranostics: Dox‐Encoded, Folate Targeted Chemotherapy with Modulation of SERS Fingerprinting for Apoptosis Toward Tumor Eradication

Ramya, Adukkadan N.; Joseph, Manu M.; Maniganda, Santhi; Karunakaran, Varsha; Sreelekha, T.T.; Maiti, Kaustabh Kumar

doi:10.1002/smll.201700819

Cited by 54 publications

(60 citation statements)

References 39 publications

(52 reference statements)

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“…Chitosan coating also prevents premature release of the entrapped drugs to avoid off‐target toxicity. [ 19 ] As the next step, targeting ability of the dual drug‐loaded nano vehicle harboring different functional groups were compared against drugs alone (Dox +TQR) and liposomal Dox (Lipodox) on FR‐positive Dox‐sensitive cancer cells, FR‐positive Dox‐resistant cancer cells, FR‐negative cancer cells, normal cells, and cancer spheroids by cytotoxicity evaluation. When indiscriminate cytotoxicity was demonstrated by bare drugs, Lipodox and MSN‐Mn‐CS; the targeted nano vehicles displayed selective toxicity (Figure S12a–j, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…To gather information about the mechanistic action of TTNV, various apoptosis assays were performed on cells and spheroids as described before. [ 19,49 ] Atomic force microscopy was also employed to visualize the morphological changes, and eventually, SERS was utilized to decipher the apoptotic molecular changes in a label‐free fashion. The influence caspases were determined using caspase profiling kit (Clontech, Mountain View, CA) and cell cycle analysis was also performed.…”

Section: Methodsmentioning

confidence: 99%

“…[ 50 ] Finally, a semi‐quantitative analysis of 43 human apoptosis markers was performed using the human apoptosis antibody array membrane (ab134001, Abcam, Cambridge, MA) as mentioned before. [ 19 ] The experimental details are described in the Supporting Information 7.…”

Section: Methodsmentioning

confidence: 99%

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Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

Joseph

Ramya

Vijayan

et al. 2020

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The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug‐resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese‐doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co‐loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual‐targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface‐enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN‐Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR‐positive syngeneic and CSC‐rich human xenograft murine models is associated with a tumor‐targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug‐loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe‐out of tumor reinitiating cancer stem cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

Joseph

Ramya

Vijayan

et al. 2020

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“…The sample sizes were chosen based on preliminary data from our pilot experiments and previous publications in the literature 3 , 8 , 10 . All quantitative data was presented as mean ± standard deviation.…”

Section: Methodsmentioning

confidence: 99%

ZnO-based multifunctional nanocomposites to inhibit progression and metastasis of melanoma by eliciting antitumor immunity via immunogenic cell death

Zhang

Guo²,

Liu³

et al. 2020

Theranostics

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Rationale: The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Methods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO 2 @DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed. The induced anti-tumor immunity was determined by analyzing immune cell profile in tumor in vivo and molecular mechanism were identified by detecting expression of immunogenic cell death (ICD) markers in vitro . Moreover, mice models of unilateral and bilateral subcutaneous melanoma and lung metastasis were established to evaluate the antitumor effects. Results: As an efficient drug carrier, ZnO-capped NPs guarantee a high DOX payload and an in vitro , efficient release of at pH 5.0. In murine melanoma models, the nanocomposite can significantly inhibit tumor growth for a short period upon low-power laser irradiation. Importantly, ZnO NPs not only demonstrate preferential selectivity for melanoma cells but can also induce ICD. Meanwhile, AuNP@mSiO 2 -based photothermal therapy (PTT) and DOX are directly cytotoxic towards cancer cells and demonstrate an elevated ICD effect. The induced ICD promotes maturation of dendritic cells, further stimulating the infiltration of effector T cells into tumor sites, preventing tumor growth and distant lung metastases. Conclusions: This study highlights the novel mechanism of ZnO-triggered anti-tumor immunity via inducing ICD. Additionally, we shed light on the multifunctionality of nanocomposites in delivering localized skin tumor therapy as well as inhibiting metastatic growth, which holds great promise in clinical applications.

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“…21 Folic acid (FA) is a prominent targeting molecule capable of specific interaction with FA receptor, which is also overexpressed in many kinds of tumor cells. 13,[22][23][24] Despite there being many studies about nanoparticles that use HA and FA as targeting ligands to gain dual-CD44 and FA receptor-targeting ability in tumor delivery systems, other hydrophobic cores such as octadecyl were used in these reports. [25][26][27][28] Most of the hydrophobic cores in these reports were long-chain polymers.…”

Section: Introductionmentioning

confidence: 99%

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

Yang¹,

Lan²,

Kang³

et al. 2018

IJN

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IntroductionA reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers.Materials and methodsHA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated.ResultsDOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (−6.7 to −31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 μg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice.ConclusionHA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.

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Emergence of Gold‐Mesoporous Silica Hybrid Nanotheranostics: Dox‐Encoded, Folate Targeted Chemotherapy with Modulation of SERS Fingerprinting for Apoptosis Toward Tumor Eradication

Cited by 54 publications

References 39 publications

Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

ZnO-based multifunctional nanocomposites to inhibit progression and metastasis of melanoma by eliciting antitumor immunity via immunogenic cell death

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

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