A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy

Abstract

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

Recent Progress in Red Blood Cells-Derived Particles as Novel Bioinspired Drug Delivery Systems: Challenges and Strategies for Clinical Translation

“…Studies have also shown near infrared (NIR) light-initiated and pH-triggered drug release. Drug release studies by many researchers have established that RBC-based drug delivery systems are advantageous in terms of prolonged circulation time and sustained release ( Zhang et al, 2021 ).…”

“…Combinatorial therapy involving two therapies at the same time is been carried out to achieve better efficacies. Doxorubicin (DOX)-loaded into hollow prussian blue nanoparticle ( Chen et al, 2017 ), paclitaxel and IR-780 co-loaded in lipid multi-chambered nanoparticles ( Zhang et al, 2021 ) and DOX-loaded hollow copper sulfide (CuS) nanoparticles ( Wang et al, 2018 ) were administered for light activated combinatorial therapies of cancer. All these nanoparticles were RBC-cloaked helping them to escape from the reticuloendothelial system (RES) and immune evasion, achieving longer circulation.…”

Cell-derived membrane biomimetic nanocarriers for targeted therapy of pulmonary disease

“…For example, to enhance the specifical targeting ability to non-small cell lung cancer cells (A549) with high expression of CD44, hyaluronic acid (HA), the receptor of CD44, was applied to insert into RBCm. ( Zhang et al, 2021c ).…”

“… Strategy Cell membrane Modifier Nanoparticle Effects Ref. Lipid insertion RBC HA-DOPE PTX, IR780 Actively targeting A549 cells ( Zhang et al, 2021c ) RBC RGD-PEG-DSPE CS-6, DOX Actively targeting TNBC cells ( Fan et al, 2020 ) RBC RGD-PEG-DSPE Black phosphorus Improving tumor targeting by specifically recognizing ανβ 3 ( Zhong et al, 2021 ) RBC cRGD-PEG-DSPE DACHPt, ICG Actively targeting cancer tissues, enhancing tumor-specific cellular uptake ( Liu et al, 2018b ) RAW 264.7 T7-PEG-DSPE Saikosaponin D/PLGA Targeting ligands transfer ferritin receptors overexpressed in tumor cells ( Sun et al, 2020 ) RBC DIR PTX-PN Providing powerful heat energy and promoting the release of core drugs under laser irradiation ( Su et al, 2016 ) A549 Liposome with MMP-9-sensitive peptide PC@CO-LC Promoting tumor cell penetration, pH triggered membrane rupture and drug release ( Zhang et al, 2021b ) Membrane hybridization RBC NCI-H1299 lung cancer cell PLGA/DOTAP/SAHA Prolonging blood circulation time and homotype targeting of metastatic cells ( Peng et al, 2021 ) 4T1 RAW 264.7 DOX/PLGA Accumulating at inflammation sites and targeting specific metastasis ( Gong et al, 2020 ) Metabolic engineering 4T1 Azide-cho, anti-CD205 MNCs Preferentially recognized by CD8+ dendritic cells ( …”

Safety of Lavender Oil-Loaded Niosomes for In Vitro Culture and Biomedical Applications

“…They can also be used in targeted delivery applications to uptake the drugs to specific sites. Furthermore, the ease of large-scale manufacturing and storage, improved stability, and healthy yet low-cost components have made niosomes an appealing alternative to conventional micro-and nano-encapsulation methods [14][15][16][17][18][19].…”