The design of a drug‐delivery system based on bioconjugated, pH‐responsive microgels is demonstrated. Microgels loaded with the anticancer drug Doxorubicin are introduced into the HeLa tumor cells by means of receptor‐ mediated endocytosis. Changes in pH within the intracellular environment induce shrinkage of microgels, triggering the drug release into the cells. The microgel described in this work shows enhanced cytotoxicity to HeLa cells (see Figure).

We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.

Semiconductor quantum dots (QDs) are a new generation of inorganic probes with advantageous properties over traditional organic-only probes for biological applications. A major hurdle in the use of QDs for biology is the inability of the hydrophobically synthesized QDs to interface with aqueous environments. There have been tremendous advances in the surface modification of hydrophobic QDs. However, none of the current techniques fits all of the criteria for an ideal QD coating for biological applications (e.g., maintain the small size and optical properties of QDs, have low nonspecific binding) while providing cost-effective, easy preparation on a large scale. We developed a highly stable biocompatible coating for the surface of ZnS-capped CdSe QDs that maintains all of the hydrophobiccoated QD optical properties. These QDs are prepared by first coating them with mercaptoundecanoic acid and are further cross-linked with the amino acid lysine in the presence of dicyclohexylcarbodiimide to form a stable hydrophilic shell. The surface contains carboxylic acid and amino functional groups for conjugation to biomolecules. Using a dynamic light scattering method, we found that the hydrodynamic diameter of these surface-modified QDs is approximately 20 nm. We demonstrated the feasibility of preparing >400 mg of the biocompatible QDs and the successful conjugation of proteins onto their surface. Finally, we characterized the QD stability and optical properties in various biologically relevant environments.

Signal processing methods and constraints for discerning the fluorescence signals of the QD‐barcodes are explored. QD‐barcodes and their corresponding fluorescence spectra (see figure) require signal processing algorithms in order to be uniquely identified. Using these algorithms, we determined the number of available barcodes for use in biological detection. We also studied the impact of chemical constraints such as buffer and pH level on the barcode and read‐out design.

No abstract