Despite great therapeutic effect of Abraxane^®, complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel (PTX) nanoparticles (NPs). Herein, we reported that an albumin-binding prodrug, phenylboronic acid-conjugated PTX (P-PTX), can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method. The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions. We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nano-precipitation approach, achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane^®. Furthermore, the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment, increased the maximum tolerated dose of PTX, remarkably suppressed the growth of breast tumor and lung metastasis, and prolonged survival of melanoma tumors-bearing mice. Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs, and provides potent strategy for the rational design of albumin-based antitumor nanomedicines.

Oncolytic virotherapy (OVT) is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus (OV)-mediated immunostimulation. Notably, talimogene laherparepvec (T-Vec) developed by the Amgen company in 2015, is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment. However, the systemic administration of OVs still faces huge challenges, including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy. Recently, state-of-the-art progress has been made in the development of systemic delivery of OVs, which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery. Herein, this review describes the general characteristics of OVs, focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT. The emerging multiple systemic administration approaches of OVs are summarized in the past five years. In addition, the combination treatments between OVT and traditional therapies (chemotherapy, thermotherapy, immunotherapy, and radiotherapy, etc.) are highlighted. Last but not least, the future prospects and challenges of OVT are also discussed, with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.