Reconstituted high density lipoprotein (rHDL), a versatile drug delivery nanoplatform for tumor targeted therapy

Mei, Yijun; Tang, Lu; Xiao, Qiaqia; Zhang, Ziqi; Zhang, Ziyao; Zang, Jing; Zhou, Jianping; Wang, Ying; Wang, Wei; Ren, Min

doi:10.1039/d0tb02139c

Cited by 34 publications

(27 citation statements)

References 201 publications

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“…Among the latter, diseases of the central nervous system are of special interest because of the tightness of the BBB. As HDL-like nanoparticles can be artificially reconstituted, a better understanding of transendothelial HDL transport also opens avenues towards improved delivery of tracers and drugs into various tissues for diagnostics and therapy, respectively [ 185 , 186 , 187 , 188 ].…”

Section: Discussionmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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The vascular endothelium serves as a barrier between the intravascular and extravascular compartments. High-density lipoproteins (HDL) have two kinds of interactions with this barrier. First, bloodborne HDL must pass the endothelium to access extravascular tissues, for example the arterial wall or the brain, to mediate cholesterol efflux from macrophages and other cells or exert other functions. To complete reverse cholesterol transport, HDL must even pass the endothelium a second time to re-enter circulation via the lymphatics. Transendothelial HDL transport is a regulated process involving scavenger receptor SR-BI, endothelial lipase, and ATP binding cassette transporters A1 and G1. Second, HDL helps to maintain the integrity of the endothelial barrier by (i) promoting junction closure as well as (ii) repair by stimulating the proliferation and migration of endothelial cells and their progenitor cells, and by preventing (iii) loss of glycocalix, (iv) apoptosis, as well as (v) transmigration of inflammatory cells. Additional vasoprotective functions of HDL include (vi) the induction of nitric oxide (NO) production and (vii) the inhibition of reactive oxygen species (ROS) production. These vasoprotective functions are exerted by the interactions of HDL particles with SR-BI as well as specific agonists carried by HDL, notably sphingosine-1-phophate (S1P), with their specific cellular counterparts, e.g., S1P receptors. Various diseases modify the protein and lipid composition and thereby the endothelial functionality of HDL. Thorough understanding of the structure–function relationships underlying the multiple interactions of HDL with endothelial cells is expected to elucidate new targets and strategies for the treatment or prevention of various diseases.

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Section: Discussionmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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“…In addition, no obvious drug leakage is identified in the rHDL encapsulated delivery system, which is suitable for enhancing the stability and solubility of some insoluble drugs, changing the pharmacokinetic parameters, and prolonging the circulation time [ 79 ]. Besides, rHDL itself can also exert a direct effect on the tumor cells; the main component apoA-I exhibits anti-neoplastic biological effects indirectly via alterations in the functions of macrophages and other immune cells in vivo [ 80 ]. Therefore, to overcome the physicochemical limitations of free drugs, including poor solubility and instability, decreasing immune clearance, off-target deposition and other disadvantages, exploring the bio-derived NPs like rHDL is necessary [ 81 ].…”

Section: Reconstituted High-density Lipoprotein (Rhdl)mentioning

confidence: 99%

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Tang

Zhao

et al. 2021

Pharmaceutics

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The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

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“…Nano-based delivery systems hold an advantage over conventional chemotherapy in that they can transport therapeutic agents preferentially to malignant tumors due to the enhanced permeability and retention (EPR) effect, preventing healthy tissues from doselimiting side effects. [11][12][13] TME is a complex microenvironment composed of a heterogeneity nature of tumors, which causes several insurmountable barriers and greatly hampers the medical performance in cancer therapy. For instance, the abnormal vasculature in tumor sites contributes to ineffective targeting in some cases; the tumor hypoxia can dramatically blunt the response of tumor…”

Section: Nanoparticles Designed To Remodel Tumor Microenvironmentmentioning

confidence: 99%

Nanoparticle-Mediated Targeted Drug Delivery to Remodel Tumor Microenvironment for Cancer Therapy

Tang¹,

Mei²,

Shen³

et al. 2021

IJN

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Advanced research has revealed the crucial role of tumor microenvironment (TME) in tumorigenesis. TME consists of a complicated network with a variety of cell types including endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs) as well as the extracellular matrix (ECM). The TME-constituting cells interact with the cancerous cells through plenty of signaling mechanisms and pathways in a dynamical way, participating in tumor initiation, progression, metastasis, and response to therapies. Hence, TME is becoming an attractive therapeutic target in cancer treatment, exhibiting potential research interest and clinical benefits. Presently, the novel nanotechnology applied in TME regulation has made huge progress. The nanoparticles (NPs) can be designed as demand to precisely target TME components and to inhibit tumor progression through TME modulation. Moreover, nanotechnology-mediated drug delivery possesses many advantages including prolonged circulation time, enhanced bioavailability and decreased toxicity over traditional therapeutic modality. In this review, update information on TME remodeling through NPs-based targeted drug delivery strategies for anticancer therapy is summarized.

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Reconstituted high density lipoprotein (rHDL), a versatile drug delivery nanoplatform for tumor targeted therapy

Abstract: rHDL is a synthesized drug delivery nanoplatform exhibiting excellent biocompatibility, which possesses most of HDL’s advantages, shows almost no toxicity and can be degraded to non-toxic substances in vivo. Recently,...

Cited by 34 publications

References 201 publications

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Nanoparticle-Mediated Targeted Drug Delivery to Remodel Tumor Microenvironment for Cancer Therapy

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