Figure 4: VBPs to Overcome Traditional Cancer Therapy Challenges.
(A) Left. Intravascular barrier, endothelial barrier and extracellular matrix (ECM) barrier limit the bioavailability of therapeutics. (A) Right. VBPs protect cargoes from intravascular barrier. Cell-penetrating peptides and ultrasonic stimulation of microbubbles facilitate VBP penetration through endothelial barrier. VBPs induce cell fusion and actin polymerization to overcome ECM barrier. (B) Left. Abnormal transporter expression keeps therapeutic drugs or toxins out of the tumor cells and pro-survival mediate tumor cell survival. (B) Right. Retention of toxins and RNAi of pro-survival proteins in the tumor cells promote cell death. (C) Left. Cytokines secreted by tumor cells inhibit cytotoxic T cells and natural killer (NK) cells and activate tumor associated macrophages (TAM) and regulatory T cells (Treg). Immune checkpoint proteins on tumor cells inhibit T cells. (C) Right. Coadministration of VBP and checkpoint inhibitors activate immune cells to kill tumor cells. (D) Left. Cancer stem cells (CSCs) are resistant to chemotherapy, radiotherapy, and immunotherapy and promote angiogenesis to leave primary tumor site for metastasis. (D) Right. CSCs and their vasculatures are targeted by VBPs.