“… 69 , 83 , 84 Furthermore, abnormal ECM, together with the increased IFP, makes lipoplexes almost motionless in the periphery of the tumor. 85 Figure 2 Illustration of Tumor Microenvironment Vascular abnormalities and lack of lymphatic drainage allow CLs to accumulate in tumor, but dense extracellular matrix and increased interstitial fluid pressure prevent the particles from penetrating deeper into the tumor. …”
Section: Main Textmentioning
confidence: 99%
“… 84 This is very exciting news for scientists to design a highly effective tumor-permeable gene delivery system, because it allows nanomedicines to target the vascular endothelial cells and trigger adsorption or receptor-mediated endocytosis for exocytosis to the adjacent cell on the other side without size limitation. 85 …”
Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors
in vivo
. Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs
in vivo
, which may provide guidance for their preclinical studies.
“… 69 , 83 , 84 Furthermore, abnormal ECM, together with the increased IFP, makes lipoplexes almost motionless in the periphery of the tumor. 85 Figure 2 Illustration of Tumor Microenvironment Vascular abnormalities and lack of lymphatic drainage allow CLs to accumulate in tumor, but dense extracellular matrix and increased interstitial fluid pressure prevent the particles from penetrating deeper into the tumor. …”
Section: Main Textmentioning
confidence: 99%
“… 84 This is very exciting news for scientists to design a highly effective tumor-permeable gene delivery system, because it allows nanomedicines to target the vascular endothelial cells and trigger adsorption or receptor-mediated endocytosis for exocytosis to the adjacent cell on the other side without size limitation. 85 …”
Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors
in vivo
. Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs
in vivo
, which may provide guidance for their preclinical studies.
“…Despite the promising results first observed in preclinical studies, this effect has turned out to be quite limited in clinical trials as it varies between both patients and tumor types, and even within the same patient or tumor type over time [116,118,124]. The extravasation from blood vessels in the tumor interstitium is a nonspecific process that is the rate-limiting factor of nanocarrier localization [116,117,124]. Moreover, solid tumors are difficult for the nanocarrier to penetrate and diffuse into [116,117,124].…”
“…The extravasation from blood vessels in the tumor interstitium is a nonspecific process that is the rate-limiting factor of nanocarrier localization [116,117,124]. Moreover, solid tumors are difficult for the nanocarrier to penetrate and diffuse into [116,117,124]. Size, shape, and surface chemistry have been identified as the major characteristics responsible for nanomedicine diffusion inside the tumor mass [115][116][117]124].…”
“…Moreover, solid tumors are difficult for the nanocarrier to penetrate and diffuse into [116,117,124]. Size, shape, and surface chemistry have been identified as the major characteristics responsible for nanomedicine diffusion inside the tumor mass [115][116][117]124]. Therefore, many nonspecific factors (e.g.…”
Introduction: Since 1968, inhaled chemotherapy has been evaluated and has shown promising results up to phase II but has not yet reached the market. This is due to technological and clinical challenges that require to be overcome with the aim of optimizing the efficacy and the tolerance of drug to reopen new developments in this field. Moreover, recent changes in the therapeutic standard of care for treating the patient with lung cancer also open new opportunities to combine inhaled chemotherapy with standard treatments. Areas covered: Clinical and technological concerns are highlighted from the reported clinical trials made with inhaled cytotoxic chemotherapies. This work then focuses on new pharmaceutical developments using dry powder inhalers as inhalation devices and on formulation strategies based on controlled drug release and with sustained lung retention or based on nanomedicine. Finally, new clinical strategies are described in regard to the impact of the immunotherapy on the patient's standard of care. Expert opinion: The choice of the drug, inhalation device, and formulation strategy as well as the position of inhaled chemotherapy in the patient's clinical care are crucial factors in optimizing local tolerance and efficacy as well as in its scalability and applicability in clinical practice.
Extracellular vesicles (EVs) have emerged as novel diagnostic and therapeutic approaches for cardiovascular diseases. EVs derived from various origins exhibit distinct effects on the cardiovascular system. However, the application of native EVs is constrained due to their poor stabilities and limited targeting capabilities. Currently, targeted modification of EVs primarily involves genetic engineering, chemical modification (covalent, non‐covalent), cell membrane modification, and biomaterial encapsulation. These techniques enhance the stability, biological activity, target‐binding capacity, and controlled release of EVs at specific cells and tissues. The diverse origins of cardioprotective EVs are covered, and the applications of cardiac‐targeting EV delivery systems in protecting against cardiovascular diseases are discussed. This review summarizes the current stage of research on the potential of EV‐based targeted therapies for addressing cardiovascular disorders.
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