Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to <2.0 μg/mL for the aqueous solubility of the drug alone. Drug release studies indicated that PTX released from these nanostructures was defined through a structure-function relationship, whereby the half-life of sustained PTX release was doubled through cross-linking of the micellar structure to form SCKs. In vitro, physically loaded micellar and SCK nanotherapeutics demonstrated IC50 values against osteosarcoma cell lines, known to metastasize to the lungs (CCH-OS-O and SJSA), similar to the pharmaceutical Taxol formulation. Evaluation of these materials in vivo has provided an understanding of the effects of nanoparticle structure-function relationships on intratracheal delivery and related biodistribution and pharmacokinetics. Overall, we have demonstrated the potential of these novel nanotherapeutics toward future sustained release treatments via administration directly to the sites of lung metastases of osteosarcoma.

Although nanomedicines have been pursued for nearly 20 years, fundamental chemical strategies that seek to optimize both the drug and drug carrier together in a concerted effort remain uncommon yet may be powerful. In this work, two block polymers and one dimeric prodrug molecule were designed to be coassembled into degradable, functional nanocarriers, where the chemistry of each component was defined to accomplish important tasks. The result is a poly(ethylene glycol) (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic poly(d-glucose carbonate) micelle (diPTX@CPGC). These nanostructures showed tunable sizes and surface charges and displayed controlled PTX drug release profiles in the presence of reducing agents, such as glutathione (GSH) and dithiothreitol (DTT), thereby resulting in significant selectivity for killing cancer cells over healthy cells. Compared to free PTX and diPTX, diPTX@CPGC exhibited improved tumor penetration and significant inhibition of tumor cell growth toward osteosarcoma (OS) lung metastases with minimal side effects both in vitro and in vivo, indicating the promise of diPTX@CPGC as optimized anticancer therapeutic agents for treatment of OS lung metastases.

Fundamental studies that gain an understanding of the tunability of physical properties of natural product-based polymers are vital for optimizing their performance in extensive applications. Variation of glass transition temperature (T g) was studied as a function of the side chain structure and molar mass for linear poly­(glucose carbonate)­s. A remarkable range of T g values, from 38 to 125 °C, was accomplished with six different alkyloxycarbonyl side chains. The impact of molar mass on T g was investigated for two series of polymers and discrete oligomers synthesized and fractionated with precise control over the degrees of polymerization. The T g was found to be greatly influenced by a synergistic effect of the flexibility and bulkiness of the repeating unit side chain, as well as the chain end relative free volume. This work represents an important advance in the development of glucose-based polycarbonates, as materials that possess high degrees of functionalizability to be capable of exhibiting diversified physicochemical and thermal properties by simple side chain modification.

Nanoparticles have been widely used for preclinical cancer imaging. However, their successful clinical translation is largely hampered by potential toxicity, unsatisfactory detection of malignancy at early stages, inaccurate diagnosis of tumor biomarkers and histology for imagingguided treatment. Herein, a targeted and in vivo copper nanocluster (CuNC) is reported with high potential to address these challenges for future translation. Its ultrasmall structure enables efficient renal/bowel clearance, minimized off-target effects in non-targeted organs, and low non-specific tumor retention. The pH-dependent in vivo dissolution of CuNCs affords minimal toxicity and potentially selective drug delivery to tumors. The intrinsic radiolabeling through the direct addition of 64 Cu into CuNC ( 64 Cu-CuNCs-FC131) synthesis offers high specific activity for sensitive and accurate detection of CXCR4 via FC131 directed targeting in novel triple negative breast cancer (TNBC) patient-derived xenograft mouse models and human TNBC tissues. In *

In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.