An ideal nanotherapeutic should enhance therapeutic efficacy of the drug while reducing side effects. This work reports development of a nanotherapeutic utilizing hyperbranched polymers as a platform for conjugating doxorubicin (DOX) and camptothecin (CPT) as potential synergistic therapies. The carrier also includes cyanine‐5 (Cy5) as an imaging tracer to monitor distribution and efficacy of the therapeutic, and a bispecific antibody (BsAb) as a cell targeting agent to increase accumulation and specificity for tumor tissue. The synergism of this drug combination is investigated by utilizing both redox‐ and hydrolytic release mechanisms of CPT and DOX, respectively. Drug release and cellular uptake studies confirm the proposed delivery mechanisms and subsequent intracellular trafficking of the drugs. In this particular case, a superadditive effect is observed in vitro for the two drugs when delivered by nanocarrier. This is enhanced when the carrier is targeted to epidermal growth factor receptor (EGFR) that is upregulated in the tumors. Moreover, tumor regression studies show that the synergistic therapeutic effect of combination nanocarriers has greater inhibition of xenograft tumor growth compared to treatments that deliver DOX or CPT alone, suggesting that codelivery of dual therapeutics using modular hyperbranched polymer carriers offers unique potential to regulate tumor growth.

Targeted nanomedicines offer many advantages over macromolecular therapeutics that rely only on passive accumulation within the tumour environment. The aim of this work was to investigate the in vivo anticancer efficiency of polymeric nanomedicines that were conjugated with peptide aptamers that show high affinity for receptors on many cancer cells. In order to assess the ability for the nanomedicine to treat cancer and investigate how structure affected the behavior of the nanomedicine, three imaging modalities were utilized, including in vivo optical imaging, multispectral optoacoustic tomography (MSOT) and ex vivo confocal microscopy. An 8-mer (A8) or 13-mer (A13) peptide aptamer that have been shown to exhibit high affinity for heat shock protein 70 (HSP70) was covalently-bound to hyperbranched polymer (HBP) nanoparticles with the purpose of both cellular targeting, as well as the potential to impart some level of chemo-sensitization to the cells. Furthermore, doxorubicin was bound to the polymeric carrier as the anticancer drug, and Cyanine-5.5 (Cy5.5) was incorporated into the polymer as a monomeric fluorophore to aid in monitoring the behavior of the nanomedicine. Enhanced tumour regression was observed in nude mice bearing MDA-MB-468 xenografts when the nanocarriers were targeted using the peptide ligands, compared to control groups treated with free DOX or HBP without aptamer. The accumulated DOX level in solid tumours was 5.5 times higher in mice treated with the targeted therapeutic, than mice treated with free DOX, and 2.6 times higher than the untargeted nanomedicine that relied only on passive accumulation. The results suggest that aptamer-targeted therapeutics have great potential for improving accumulation of nanomedicines in tumours for therapy.

This review describes how the highly tuneable size, shape and chemical functionality of polymeric molecular imaging agents provides a means to intimately probe the various mechanisms behind disease formation and behaviour.

Development of biodegradable and functionalised face mask nonwovens to address the plastic pollution issue generated by disposable face masks.