Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response

Abstract

Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of this technique is restricted by the paucity of suitable tumorassociated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (α-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, α-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8 + T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by α-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, α-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine.

Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

“…Moreover, it is favourable to transport negatively charged nanoparticles into the lymphatic system in the interstitial fluid due to the negative charge on glycosaminoglycans in the extracellular matrix 23 . Previously, we developed a high-density lipoprotein (HDL)-mimicking peptide-phospholipid scaffold (HPPS) with hydrodynamic diameters of 10-30 nm 24 that can migrate to LNs by size-dependent passive transport 21,25 . Moreover, HPPS nanoparticles can target scavenger receptor class B type 1 (SR-B1), which is expressed on breast cancer cells 26 .…”

Redox-Sensitive Nanocomplex for Targeted Delivery of Melittin

“…Due to the same reason, the non-specific cytolytic activity of melittin could result in severe off-target effects, such as hemolysis (lysis of red blood cells), when administrated intravenously. To make melittin druggable and safer, many approaches have been explored through environmental liable modification [ 16 , 17 ] or nanoencapsulation [ 18 , 19 , 20 ]. Previously, our group utilized a dual-secured “nanobee” technology with the help of succinic anhydride-modified glycol chitosan (SAMGC), and disulfide bonds successfully increased the therapeutic window of melittin to 10 µM [ 21 ].…”

Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice

“…The cytotoxicity difference of Ir-cR8 towards normal cell lines and cancer cell lines may result from the more negative charges in the membrane surface of the cancer cells than in normal cells, which induced a stronger electrostatic interaction between Ir-cR8 and the cancer cell membrane. 68 More interestingly, the Ir-cR8 treated cancer cells manifested oncotic cell death which was likely to be a form of immunogenic cell death because of its eruptive leakage of cell content. 69 Dendritic cells (DCs) are crucial antigen-presenting cells and play key roles in initiating and regulating innate and acquired immunities, thus they have great potential for inducing efficient anti-tumour immunity by manipulating the DCs.…”