Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice

Bastaki, Shima; Aravindhan, Surendar; Saheb, Nasrin Ahmadpour; Kashani, Mahsa Afsari; Dorofeev, A.E.; Kiani, Fariba Karoon; Jahandideh, Hediyeh; Dargani, Farzaneh Beigi; Aksoun, Mohsen; Nikkhoo, Afshin; Masjedi, Ali; Mahmoodpoor, Ata; Ahmadi, Majid; Aghdash, Simin Namvar; Jadidi‐Niaragh, Farhad

doi:10.1016/j.lfs.2020.118847

Cited by 53 publications

(17 citation statements)

References 80 publications

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“…In fact, similar approaches (but using antibodies instead of siRNA) tackled by Allison and Honjo were so revolutionary and had so much impact that they resulted in the concession of the 2018 Nobel Prize in Physiology and Medicine to the abovementioned investigators. As immunotherapeutic agents are on the rise, Bastaki et al contributed to the field with their experiments in the delivery of siRNAs to silence programmed cell death-ligand 1 (PD-L1) and signal transducer and activator of transcription-3 (STAT-3) genes [181]. By doing so, they designed TMC and thiolated chitosan NPs to hold the desired siRNA, as shown in Figure 15.…”

Section: Thiomer-based Conjugates For Sirna Administrationmentioning

confidence: 99%

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Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

Grosso

de-Paz

2021

Pharmaceutics

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Thiomers (or thiolated polymers) have broken through as avant-garde approaches in anticancer therapy. Their distinguished reactivity and properties, closely linked to their final applications, justify the extensive research conducted on their preparation and use as smart drug-delivery systems (DDSs). Multiple studies have demonstrated that thiomer-rich nanoformulations can overcome major drawbacks found when administering diverse active pharmaceutical ingredients (APIs), especially in cancer therapy. This work focuses on providing a complete and concise review of the synthetic tools available to thiolate cationic and anionic polymers, in particular chitosan (CTS) and hyaluronic acid (HA), respectively, drawing attention to the most successful procedures. Their chemical reactivity and most relevant properties regarding their use in anticancer formulations are also discussed. In addition, a variety of NP formation procedures are outlined, as well as their use in cancer therapy, particularly for taxanes and siRNA. It is expected that the current work could clarify the main synthetic strategies available, with their scope and drawbacks, as well as provide some insight into thiomer chemistry. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of cancer.

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Section: Thiomer-based Conjugates For Sirna Administrationmentioning

confidence: 99%

“…The in vivo experiments shed light on promising results regarding significant downregulation of PD-L1 and STAT-3 genes. Consequently, important restriction of tumor growth was achieved: proliferation, migration, and angiogenesis of breast and melanoma cancer cells lines were strikingly lowered [181].…”

Section: Thiomer-based Conjugates For Sirna Administrationmentioning

confidence: 99%

Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

Grosso

de-Paz

2021

Pharmaceutics

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“…A recent example is represented by the synthesis of hyaluronic acid-derivatized PLGA nanoparticles to actively target the CD44 receptors present on the surface of breast cancer cells and selectively delivering the antitumoral molecule tamoxifen, well known to be active against estrogen receptor-positive breast cancer cells, thus reducing the correlated side-effects [ 26 ]. Among the different peptides implemented as targeting molecules in nanoparticle development, an important role is represented by the HIV transcriptional activator protein TAT peptide (TAT), which has been widely used as an uptake enhancer for cancer cells [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia

et al. 2021

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The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.

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“…The micelle carrier loaded with triptorelin and HIF-1 siRNA showed effective cell internalization, inhibited the expression of HIF-1α and VEGF in RB cells, leading to inhibition of the HIF-1α/VEGF/VEGFR signaling pathway, and the proliferation, migration, and invasion of vascular endothelial cells. Bastaki et al (2021) generated trimethyl chitosan and thiolated chitosan nanoparticles (NPs) conjugated with HIV-1-derived TAT peptide and HA (hyaluronic acid). These NPs exhibited prominent physicochemical characteristics, notable siRNA encapsulation, serum stability, non-toxicity, controlled siRNA release, and extensive cellular uptake by cancer cells.…”

Section: Non-coding Rnas To Regulate Tumor Angiogenesismentioning

confidence: 99%

Non-coding RNAs in Regulating Tumor Angiogenesis

Song

Guo

Song

et al. 2021

Front. Cell Dev. Biol.

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Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins, but perform biological functions in various physiological and pathological processes, including cancer formation, inflammation, and neurological diseases. Tumor blood vessels are a key target for cancer management. A number of factors regulate the angiogenesis of malignant tumors. NcRNAs participate in the regulation of tumor angiogenesis. Abnormal expression of ncRNAs act as tumor suppressors or oncogenes to affect the development of tumors. In this review we summarized the biological functions of ncRNAs, and discussed its regulatory mechanisms in tumor angiogenesis. This article will provide new insights for the research of ncRNAs in tumor angiogenesis.

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Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice

Cited by 53 publications

References 80 publications

Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia

Non-coding RNAs in Regulating Tumor Angiogenesis

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