Hybrid liposome–erythrocyte drug delivery system for tumor therapy with enhanced targeting and blood circulation

Abstract

Liposome, a widely used drug delivery system (DDS), still shows several disadvantages such as dominant clearance by liver and poor target organ deposition. To overcome the drawbacks of liposomes, we developed a novel red blood cell (RBC)-liposome combined DDS to modulate the tumor accumulation and extend the blood circulation life of the existing liposomal DDS. Here, RBCs, an ideal natural carrier DDS, were utilized to carry liposomes and avoid them undergo the fast clearance in the blood. In this study, liposomes could either absorbed onto RBCs’ surface or fuse with RBCs’ membrane by merely altering the interaction time at 37 °C, while the interaction between liposome and RBCs would not affect RBCs’ characteristics. In the in-vivo anti-tumor therapeutic efficacy study, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes attached onto RBCs’ surfaces exhibited lung targeting effect (via RBC-hitchhiking approach) and reduced clearance in the liver, while DPPC liposomes fused with RBCs had prolong blood circulation up to 48 h and no enrichment in any organ. Furthermore, 20 mol% of DPPC liposomes were replaced with pH-sensitive phospholipid 1,2-Dioleoyl-Sn-glycero-3-phosphoethanolamine (DOPE) as it could respond to the low pH tumor microenvironment and then accumulate in the tumor. The DOPE attached/fusion RBCs showed partial enrichment in lung and about 5-8% tumor accumulation, which were significantly higher than (about 0.7%) of the conventional liposomal DDS. Thus, RBC-liposome composite DDS is able to improve the liposomal tumor accumulation and blood circulation, and shows the clinical application promises of using autologous RBCs for antitumor therapy.

Glycyrrhizic Acid-Based Liposome for Tumor-Targeted Delivery of Cantharidin

“…LPs with an average particle size of 30–100 nm can effectively prevent infiltration into the capillaries while avoiding phagocytosis by the reticuloendothelial system (RES) . Moreover, spherical LPs with smaller particle size are more prone to be accumulated at solid tumor tissue through passive targeting mediated by the EPR effect, whereas LPs with larger particle size (>300 nm) tend to be captured by the RES. , Thus, GA–LP may facilitate alteration of drug transport processes in vivo to increase its accumulation in solid tumors. GA–LP was used as a nanocarrier to encapsulate CTD, and the addition of CTD caused no change in the particle size and initial morphology of the LPs.…”

Red blood cells: a potential delivery system

“…RBCm as camouflage is used to extend circulation and immune escape, while the NP core contributes to high drug loading. The coated nanoparticles include lipid multichambered nanoparticles [ 93 , 94 ], metal nanoparticles[ 10 , 68 , 95 – 98 ], polymers such as poly(lactic-co-glycolic acid) (PLGA) [ 99 , 100 ] or polyethylene glycol (PEG) [ 101 , 102 ] and some new nanomaterials like boron nitride nanospheres (BNNSs) [ 103 ], albumin[ 104 ] and so on [ 105 – 107 ]. From these results, we find that RBCm can improve the stability of NPs and avoid anaphylaxis via injection.…”

Looking back, moving forward: protein corona of lipid nanoparticles

“…7,8 Moreover, conventional liposomes can be categorized by phospholipid type into cationic, anionic and neutral liposomes. 9,10 Among them, liposomes synthesized from neutral phospholipids such as phosphatidylcholine, 11 dipalmitoyl phosphatidylcholine (DPPC), 12,13 and 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC) 14,15 as lipid materials are neutral liposomes, while N -[1(2,3-dioloyloxy) propyl]- N , N , N -trimethylammonium chloride (DOTAP) 16 and oleic acid 17 are commonly used for the preparation of cationic and anionic liposomes, respectively. Ionic-rich liposome particles repel each other due to electrostatic interaction, reducing their aggregation ability, and thus enhancing physical stability.…”