General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

Multifunctional yolk/shell-structured hybrid nanomaterials have attracted increasing interest as theranostic nanoplatforms for cancer imaging and therapy. However, because of the lack of suitable surface engineering and tumor targeting strategies, previous research has focused mainly on nanostructure design and synthesis with few successful examples showing active tumor targeting after systemic administration. In this study, we report the general synthetic strategy of chelator-free zirconium-89 （89Zr）-radiolabeled, TRC105 antibody-conjugated, silica-based yolk/sheU hybrid nanopartides for in vivo tumor vasculature targeting. Three types of inorganic nanoparticles with varying morphologies and sizes were selected as the internal cores, which were encapsulated into single hollow mesoporous silica nanosheUs to form the yolk/sheU-structured hybrid nanopartides. As a proof-of-concept, we demonstrated successful surface functionalization of the nanoparticles with polyethylene glycol, TRC105 antibody （specific for CD105/endoglin）, and ~Zr （a positron-emitting radioisotope）, and enhanced in vivo tumor vasculature-targeted positron emission tomography imaging in 4T1 murine breast tumor-bearing mice. This strategy could be applied to the synthesis of other types of yolk/shell theranostic nanoparticles for tumor- targeted imaging and drug delivery.

Phage display screening of therapeutic peptide for cancer targeting and therapy

Recently,phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018.Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process;proving to be a powerful technique in the screening of peptide with high affinity and selectivity.In this review,we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ,in vitro,in vivo,and ex vivo screening methods.We will then discuss prominent examples of solid tumor targeting-peptides;namely peptide targeting tumor vasculature,tumor microenvironment(TME)and overexpressed receptors on cancer cells identified through phage display screening.We will also discuss the current challenges and future outlook for targeting peptidebased therapeutics in the clinics.