Abstract:Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors. However, the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment (TME) and the insufficient accumulation in tumor sites. Meanwhile, the application of cholesterol and polyethylene glycol (PEG), which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,
has been questioned due to various disadvantages. Herein, w… Show more
“…Chao et al reported that, compared with non-PEGylated liposomes, PEGylated liposomes adsorbed less proteins in the blood, which mainly reduced the affinity of immunoglobulins. However, apolipoprotein E, which has been shown to retard the phagocytosis of macrophages, was not found in the protein corona of PEGylated liposomes [ 66 ]. In our work, the protein compositions in the RBCm and the blood-treated nanocarriers (LCNPs and HA&RBCm-LCNPs) were quite different (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In conclusion, the prolonged circulation of HA&RBCm-LCNPs in the blood is considered to have been achieved via the following: (1) alterations to the types rather than the amounts of proteins attached to the surface of the nanoparticles; (2) an abundance of CD47 and reduced affinity to myosins; and (3) excellent sustained-release properties. In addition, apolipoprotein E was detected in both LCNP and HA&RBCm-LCNP groups ( p > 0.05), suggesting that the circulatory properties of the tested nanocarriers are distinct from those of PEGylated nanoparticles [ 66 ].…”
Background
A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed.
Results
Herein, we designed hyaluronic acid (HA)–hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway.
Conclusions
The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.
Graphical abstract
“…Chao et al reported that, compared with non-PEGylated liposomes, PEGylated liposomes adsorbed less proteins in the blood, which mainly reduced the affinity of immunoglobulins. However, apolipoprotein E, which has been shown to retard the phagocytosis of macrophages, was not found in the protein corona of PEGylated liposomes [ 66 ]. In our work, the protein compositions in the RBCm and the blood-treated nanocarriers (LCNPs and HA&RBCm-LCNPs) were quite different (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In conclusion, the prolonged circulation of HA&RBCm-LCNPs in the blood is considered to have been achieved via the following: (1) alterations to the types rather than the amounts of proteins attached to the surface of the nanoparticles; (2) an abundance of CD47 and reduced affinity to myosins; and (3) excellent sustained-release properties. In addition, apolipoprotein E was detected in both LCNP and HA&RBCm-LCNP groups ( p > 0.05), suggesting that the circulatory properties of the tested nanocarriers are distinct from those of PEGylated nanoparticles [ 66 ].…”
Background
A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed.
Results
Herein, we designed hyaluronic acid (HA)–hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway.
Conclusions
The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.
Graphical abstract
“…It has been demonstrated that the stealth effect of NPs modified with ginsenosides reduced the adsorption of opsonins on the surface of the liposomes. Ginsenosides Rh2, Rg3 and Rg5 have shown a stealth effect due to the increased adsorption of apolipoprotein E, which can retard the absorption of macrophages to liposomes [ 25 ].…”
Section: Ginsenosidesmentioning
confidence: 99%
“…Developing a new ginsenoside DDSs has attracted wide attention in attempts to achieve synergism and detoxification, as well as to improve bioavailability. Furthermore, because of the similar structure of cholesterol and ginsenosides, the latter have been used as excipients to synthesize liposomes with simultaneous targeting ability [ 25 – 28 ]. Fig.…”
Ginsenosides, the main components isolated from Panax ginseng, can play a therapeutic role by inducing tumor cell apoptosis and reducing proliferation, invasion, metastasis; by enhancing immune regulation; and by reversing tumor cell multidrug resistance. However, clinical applications have been limited because of ginsenosides’ physical and chemical properties such as low solubility and poor stability, as well as their short half-life, easy elimination, degradation, and other pharmacokinetic properties in vivo. In recent years, developing a ginsenoside delivery system for bifunctional drugs or carriers has attracted much attention from researchers. To create a precise treatment strategy for cancer, a variety of nano delivery systems and preparation technologies based on ginsenosides have been conducted (e.g., polymer nanoparticles [NPs], liposomes, micelles, microemulsions, protein NPs, metals and inorganic NPs, biomimetic NPs). It is desirable to design a targeted delivery system to achieve antitumor efficacy that can not only cross various barriers but also can enhance immune regulation, eventually converting to a clinical application. Therefore, this review focused on the latest research about delivery systems encapsulated or modified with ginsenosides, and unification of medicines and excipients based on ginsenosides for improving drug bioavailability and targeting ability. In addition, challenges and new treatment methods were discussed to support the development of these new tumor therapeutic agents for use in clinical treatment.
“…Furthermore, Hong reported ginsenoside Rh2 could improve physical and chemical properties of phospholipid bilayer. 29 But the aforementioned compounds are triterpenoid pentacyclic saponin. The interaction of steroid pentacyclic saponin with lipid membranes remains to be investigated.…”
Introduction
As high cholesterol level has been reported to be associated with cancer cell growth and cholesterol is vulnerable to oxidation, the conventional liposomes including cholesterol in the formulation seem to be challenged. Timosaponin AIII (TAIII), as a steroid saponin from
Anemarrhena asphodeloides
Bunge, possesses a similar structure with cholesterol and exhibits a wide range of antitumor activities, making it possible to develop a TAIII-based liposome where TAIII could potentially stabilize the phospholipid bilayer as a substitution of cholesterol and work as a chemotherapeutic drug as well. Meanwhile, TAIII could enhance the uptake of doxorubicin hydrochloride (DOX) in human hepatocellular carcinoma (HCC) cells and exhibit synergistic effect. Thus, we designed a novel thermally sensitive multifunctional liposomal system composed of TAIII and lipids to deliver DOX for enhanced HCC treatment.
Methods
The synergistic effects of DOX and TAIII were explored on HCC cells and the tumor inhibition rate of TAIII-based liposomes carrying DOX was evaluated on both subcutaneous and orthotopic transplantation tumor models. TAIII-based multifunctional liposomes were characterized.
Results
Synergistic HCC cytotoxicity was achieved at molar ratios of 1:1, 1:2 and 1:4 of DOX/TAIII. TAIII-based liposomes carrying a low DOX dose of 2 mg/kg exhibited significantly enhanced antitumor activity than 5 mg/kg of DOX without detected cardiotoxicity on both subcutaneous and orthotopic transplantation tumor models. TAIII-based liposomes were characterized with smaller size than cholesterol liposomes but exhibited favorable stability. Mild hyperthermia generated by laser irradiation accelerated the release of DOX and TAIII from liposomes at tumor site, and cell permeability of TAIII enhanced uptake of DOX in HCC cells.
Conclusion
The innovative application of TAIII working as bilayer stabilizer and chemotherapeutic drug affords a stable multifunctional liposomal delivery system for synergistic therapy against HCC, which may be referred for the development of other types of saponins with similar property.
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