Ligand-targeted Particulate Nanomedicines Undergoing Clinical Evaluation: Current Status

MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

“…Many liposome-based therapies carrying chemotherapeutic drugs are currently in phase I or II clinical trials for several solid tumours [42]. However, so…”

Insight into nanoparticle cellular uptake and intracellular targeting

“…Transferrin (Tf) and TfR binding single chain antibody fragment (TfRscFv) have been used as ligands for transferrin receptor-mediated intracellular delivery of nanotherapeutics. The examples of TfR targeted nanomedicines that are at various stages of clinical trials include CALAA-01 (a four component nanomedicine in phase I clinical trial constituted by Tf-functionalized PEG, Tf and adamentane functionalized PEG, SiRNA and a cyclodextrin bearing polymer), MBP-426 (liposome based oxaliplatin loaded Tf conjugated nanomedicine in Phase II clinical trial), SGT-53 (intracellular delivery of p53 plasmid DNA using TfRscFv conjugated liposome based nanomedicine in Phase Ib clinical trial), and SGT-94 (RB94 plasmid DNA delivery using TfRscFv conjugated liposome in Phase I clinical trial) [109]. These successful examples have triggered substantial interest in the further development of TfR targeted nanomedincine.…”

“…Anti-EGFR ILs-DOX (Fab′ fragments of anti-EGFR antibody ceuximab conjugated DOX loaded immunoliposomes targeted to EGFR in Phase I clinical trial) represents a notable example of EGFR targeted nanomedicines [109]. In a recent attempt of targeting HER1, Shevtsov et al developed the superparamagnetic iron oxide nanoparticles conjugated with recombinant human epidermal growth factor (SPION-EGF) for the enhanced magnetic resonance imaging of malignant brain tumors and demonstrated more efficient tumor imaging than that of non-targeted SPION in an orthotopic model of C6 gliomas [118].…”

“…In pre-clinical studies, Lee et al demonstrated that the DOX-loaded PEG-PLGA-Au half-shell nanoparticles with Herceptin resulted in higher accumulation in tumor sites of SK-BR-3 (breast cancer cell line with high HER2 expression) bearing mice by receptor-mediated endocytosis and finally stronger therapeutic efficacy based on chemotherapy and hyperthermia compared to non-targeted nanoparticles [121]. MM302 (HER2 targeted scFv antibody fragment conjugated DOX loaded liposome) represents an example of HER2 targeted nanomedicine in Phase I clinical trial [109]. Currently, HER3, which is the only member of EGFR family lacking intrinsic tyrosine kinase activity, has gained significant interest for targeting of EGFR [122].…”

Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy

“…43 Ó 2015 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. 44 45 46 47 1. Introduction 48 Nanomedicines have been investigated for cancer therapy for 49 several decades, with several products in clinical trials or in the 50 market [1]. Safe and efficient delivery of poorly-water soluble 51 and/or low permeable chemotherapeutic drugs is still one of the 52 main tasks to be overcome by cancer medicines.…”