In designing drug carriers, the drug-to-carrier ratio is an important consideration because using high quantities of carriers can cause toxicity resulting from poor metabolism and elimination of the carriers1. However, these issues would be of less concern if both the drug and carrier possess therapeutic effects. (-)-Epigallocatechin-3-O-gallate (EGCG), which is a major ingredient of green tea, has been shown to possess anticancer effects2-7, anti-HIV effects8, neuroprotective effects9, DNA-protective effects10, etc. Here we show that sequential self-assembly of the EGCG derivative with anticancer proteins forms stable micellar nanocomplexes (MNCs), which have greater anticancer effects in vitro and in vivo than the free protein. The MNC is obtained by complexation of oligomerized EGCG with the anticancer protein, Herceptin, to form the core, followed by complexation of poly(ethylene glycol)-EGCG to form the shell. When injected into mice, the Herceptin-loaded MNC showed better tumour selectivity and growth reduction, and longer blood-half-life than free Herceptin.

Low drug loading and instability in blood circulation are two key challenges that impede the successful clinical translation of nanomedicine, as they result in only marginal therapeutic efficacy and toxic side effects associated with premature drug leakage, respectively. Herein, highly stable and ultrahigh drug loading micellar nanocomplexes (MNCs) based on the self-assembly of the anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3-O-gallate (EGCG) conjugate are developed. The formation of these MNCs is facilitated by strong favorable intermolecular interactions between the structurally similar aromatic EGCG and DOX molecules, which impart exceptionally high drug-loading capability of up to 88% and excellent thermodynamic and kinetic stability. Unlike two clinical formulations of DOX-free DOX and liposomal DOX, which are not effective below their lethal dosages, these DOX-loaded MNCs demonstrate significant tumor growth inhibition in vivo on a human liver cancer xenograft mouse model with minimal unwanted toxicity. Overall, these MNCs can represent a safe and effective strategy to deliver DOX for cancer therapy.

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3-O-gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG-b-poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumortargeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier−drug synergies with the highperformance carrier of PEG-EGCG besides tumor-targeted delivery.

One of the pathways by which cadmium enters human beings is through the consumption of agricultural products. The monitoring of cadmium has a significant role in the management of cadmium intake. Cadmium purification and quantification using immunochromatography were conducted in this study as an alternative means of cadmium analysis. The samples used in this study were rice, tomato, lettuce, garden pea, Arabidopsis thaliana (a widely used model organism for studying plants), soil, and fertilizer. The cadmium immunochromatography has been produced from the monoclonal antibody Nx2C3, which recognize the chelate form of cadmium, Cd.EDTA. The immunochromatography can be used for quantification of cadmium in a range from 0.01 to 0.1 mg/L at 20% mean coefficient of variance. A chelate column employing quaternary ammonium salts was used for the purification of cadmium from HCl extracts of samples. Recoveries of cadmium were near 100%, and the lowest recovery was 76.6% from rice leaves. The estimated cadmium concentrations from the immunochromatography procedure were evaluated by comparison with the results of instrumental analysis (ICP-AES or ICP-MS). By comparison of HCl extracts analyzed by ICP-MS and column eluates analyzed by immunochromatography of the samples, the estimated cadmium concentrations were closely similar, and their recoveries were from 98 to 116%.

The synthesis of photoresponsive oligoethers containing cinnamylidene acetic acid as telechelic endgroup was reported and high degrees of functionalization could be achieved. Such photosensitive oligomers are promising candidates as reactive precursors, for the preparation of biocompatible high molecular weight polymers and polymer networks.