Rational design of a minimalist nanoplatform to maximize immunotherapeutic efficacy: Four birds with one stone

Zhou, Shengyan; Shang, Qi; Wang, Ningning; Li, Qian; Song, Aixin; Luan, Yuxia

doi:10.1016/j.jconrel.2020.09.035

Cited by 127 publications

(67 citation statements)

References 78 publications

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“…In spite of the excellent antitumor effects, low water solubility, poor metabolic stability and bioavailability, short half-life and poor tumor targeting capability have been proven almost to be an insurmountable obstacle for clinical translations of Que (Dabeek & Marra, 2019 ). Recent progresses in nanotechnology offer more possibilities to overcome these drawbacks of drugs themselves, which can efficiently encapsulate them and ameliorate their pharmacokinetics and pharmacodynamic profiles (Zhou et al., 2020 ; Li et al., 2021a,b ; Zhang et al., 2022 ). Interestingly, nanoparticles are capable of passively accumulating into tumor sites as a result of incomplete vessels and lymphatic blockage termed as enhanced permeability and retention (EPR) effect (Fang et al., 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Zang

Meng

et al. 2022

Drug Delivery

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Lung cancer is the leading cause of cancer death world-wide and its treatment remains a challenge in clinic, especially for non-small cell lung cancer (NSCLC). Thus, more effective therapeutic strategies are required for NSCLC treatment. Quercetin (Que) as a natural flavonoid compound has gained increasing interests due to its anticancer activity. However, poor water solubility, low bioavailability, short half-life, and weak tumor accumulation hinder in vivo applications and antitumor effects of Que. In this study, we developed Que-loaded mixed micelles (Que-MMICs) assembled from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–poly(ethylene glycol)–biotin (DSPE–PEG–biotin) and poly(ethylene glycol) methyl ether methacrylate–poly[2-(dimethylamino) ethyl acrylate]–polycaprolactone (PEGMA–PDMAEA–PCL) for NSCLC treatment. The results showed that Que was efficiently encapsulated into the mixed micelles and the encapsulation efficiency (EE) was up to 85.7%. Cellular uptake results showed that biotin conjugation significantly improved 1.2-fold internalization of the carrier compared to that of non-targeted mixed micelles. In vitro results demonstrated that Que-MMICs could improve cytotoxicity (IC 50 = 7.83 μg/mL) than Que-MICs (16.15 μg/mL) and free Que (44.22 μg/mL) to A549 cells, which efficiently induced apoptosis and arrested cell cycle. Furthermore, Que-MMICs showed satisfactory tumor targeting capability and antitumor efficacy possibly due to the combination of enhanced permeability and retention (EPR) and active targeting effect. Collectively, Que-MMICs demonstrated high accumulation at tumor site and exhibited superior anticancer activity in NSCLC bearing mice model.

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Section: Introductionmentioning

confidence: 99%

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Zang

Meng

et al. 2022

Drug Delivery

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“…More importantly, DTX injection could be quickly metabolized following intravenous administration, resulting in low tumor accumulation and poor antitumor activity [7] . Therefore, drug delivery systems with high efficiency and security has always been desired for clinical chemotherapy [8 , 9] .…”

Section: Introductionmentioning

confidence: 99%

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Wang

Luo

Zhou

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

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“…Tumor cells avoid the immune response in a process known as immune evasion (Schreiber et al., 2011 ; Zhou et al., 2020 ; Ren et al., 2021 ; Zhou et al., 2021 ). The immune escape of tumor cells is divided into three stages: (1) Elimination phase: at this stage, antigen-presenting cells (APC) monitor the antigens expressed by tumors and present them to cytotoxic T cells through major histocompatibility complex (MHC) class I molecules, which is the first signal of T cell activation, then the molecule CD80/CD86 on the surface of APC combines the costimulatory molecule CD28 on the surface of T cells which forms a costimulatory signal (Murakami & Riella, 2014 ), thereby cytotoxic T cells are activated, they target and eliminate tumor cells by secreting perforin, granzyme or by the death ligand/death receptor pathway (Martinez-Lostao et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Lysosome activable polymeric vorinostat encapsulating PD-L1KD for a combination of HDACi and immunotherapy

Hou

Wang

et al. 2021

Drug Delivery

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PD-1/PD-L1 blocking therapy has become one of the most promising methods in the field of tumor treatment. However, it encounters the challenge of immune escape due to the exhaustion of T cells. Studies have shown that the epigenetic regulation drug histone deacetylase inhibitor (HDACi) may be able to reverse exhausted T cells by changing the epigenetic transcription program. Therefore, the combination of epigenetic therapy and PD-1/PD-L1 blockade therapy is expected to reverse the immune escape, whereas the overriding goal should aim at the spontaneous release and synergy of PD-1/PD-L1 blocking siRNA and HDACi. In this study, we develop PDDS{polyethylene glycol-b-asparaginate(diethylenetriamine-vorinostat), (PEG-b-P[Asp(DET-SAHA) n ] PPDS)}encapsulating siRNA-PD-L1to provide micelles siRNA-PD-L1-loaded micelles (siRNA@PPDS). Transmission electron microscope (TEM) images demonstrate that siRNA@PPDS micelles presented spherical morphology with a size of about 120 nm; hydrodynamic data analysis indicates pH sensitivity of siRNA@PPDS micelles. The experiments reveal that siRNA@PPDS micelles could be well uptaken by the tumor cells to silence the expression of PD-L1 protein in a dose-dependent manner; compared with the free SAHA, the SAHA-loaded micelles PPDS show higher cytotoxicity to induce tumor cell apoptosis and block cell cycle in G1 phase on melanoma-bearing mice, siRNA@PPDS has shown outstanding inhibition of tumor growth and pulmonary metastasis. By comprehensively activating the immune system, lysosome activable polymeric vorinostat encapsulating PD-L1KD for the combination therapy of PD-L1-KD and HDACIs can be an effective strategy to reverse the unresponsiveness of immune checkpoint inhibitors and a promising treatment to inhibit tumor growth, recurrence, and metastasis in clinic.

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Rational design of a minimalist nanoplatform to maximize immunotherapeutic efficacy: Four birds with one stone

Cited by 127 publications

References 78 publications

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Lysosome activable polymeric vorinostat encapsulating PD-L1KD for a combination of HDACi and immunotherapy

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