Mitochondria-targeting turn-on fluorescent probe for HClO detection and imaging in living cells.

Hypochlorous/hypochlorite (HClO/ClO-), one of the most important signal molecule, plays a crucial role in many cellular signaling pathways. It is reported that the HClO/ClO- level in mitochondria is important to maintain the normal mitochondrial function. Herein, we present two simple fluorescent probes BAC and mitochondria-targeting fluorescent probe TACB for the detection of ClO-. Probes BAC &TACB could be sensitively and selectivity detecting ClO- at the nanomolar levels with the detection limit of 1.64 × 10-9 M and 9.86 × 10-8 M, respectively. Additionally, probes BAC &TACB with the response unit of CO moiety could selectively detect ClO- over other various analytes such as anions, metal ions and OH, 1O2, H2O2. The response time of probe TACB for ClO- (<20 s), implying that it could offer a real-time analytical assay of ClO-. Finally, probe BAC was used for monitoring the ClO- in HEK293T cells and probe TACB could be utilized to track the fluctuations of exogenous ClO- levels in the mitochondria of Hela cells.

Preparation of hierarchical hollow CaCO3 particles and the application as anticancer drug carrier.

One-pot approach to couple the crystallization of CaCO(3) nanoparticles and the in situ symmetry-breaking assembly of these crystallites into hollow spherical shells was developed under the templating effect of a soluble starch. Further functional study using HP-a as an anticancer drug carrier (DOX) demonstrated its advantages for localizing drug release by the pH value-sensitive structure and enhancing cytotoxicity by increasing cellular uptake, perinuclear accumulation, and nuclear entry.

Preparation and characterization of thermo-responsive albumin nanospheres.

Thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-polyallylamine-conjugated albumin nanospheres (PAN), new thermal targeting anti-cancer drug carrier, was developed by conjugating poly(N-isopropylacrylamide-co-acrylamide)-block-polyallylamine (PNIPAM-AAm-b-PAA) on the surface of albumin nanospheres (AN). PAN may selectively accumulate onto solid tumors that are maintained above physiological temperature due to local hyperthermia. PNIPAM-AAm-b-PAA was synthesized by radical polymerization, and AN was prepared by ultrasonic emulsification. AN with diameter below 200 nm and narrow size distribution was obtained by optimizing the preparative conditions. Rose Bengal (RB) was used as model drug for entrapment into the AN and PAN during the particle preparation. The release rate of RB from PAN compared with AN in trypsin solution was slower, and decreased with the increase of PNIPAM-AAm-b-PAA molecular weight, which suggested that the existence of a steric hydrophilic barrier on AN made digestion of AN more difficult. Moreover, the release of RB from PAN above the cloud-point temperature (T(cp)) of PNIPAM-AAm-b-PAA became faster. This was because the density of temperature-responsive polymers on AN was not so high, so that the interspace between the polymer chains increased after they shrunk due to the high temperature. As a result, the biodegradable AN was attacked more easily by trypsin. The design of PAN overcame the disadvantages of temperature-responsive polymeric micelles.

Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer.

Early diagnosis of cancer greatly increases the chances of successful treatment by radical resection. The sensitivity of magnetic resonance imaging (MRI) techniques for detecting early stage tumors can be increased with the assistance of a positive MRI contrast agent. However, the traditional positive MRI contrast agents, such as Gd-chelates and Gd-based inorganic nanoparticles, are often limited by their cytotoxicity and low specificity. Here, we propose a new design of MRI contrast agent based on gadolinium oxide nanocrystals (GON) for targeted imaging and cancer early diagnosis with good biocompatibility. The GON were prepared using a polyol method and then encapsulated into albumin nanoparticles (AN), which were cross-linked with glutaraldehyde and found to exhibit bright and stable autofluorescence without conjugation to any fluorescent agent. After that, a target molecule, folic acid (FA), was conjugated onto the surface of the GON-loaded AN (GON-AN) to construct a GON-AN-FA composite. The as-prepared nanoparticles are biocompatible and stable in serum. The results of MRI relaxation studies show that the longitudinal relaxivities (r1) of GON-AN (11.6 mM-1 s-1) and GON-AN-FA (10.8 mM-1 s-1) are much larger than those of traditional positive MRI contrast agents, such as Magnevist (3.8 mM-1 s-1). The results of cell viability assays indicate that GON-AN and GON-AN-FA are almost non-cytotoxic. Furthermore, the specificities of GON-AN and GON-AN-FA were evaluated with two kinds of cancer cells which overexpress folate receptor alpha (FRα). The results reinforce that the autofluorescent GON-AN-FA is able to target cancer cells via recognition of the ligand FA and the receptor FRα. Therefore, our autofluorescent GON-AN-FA possessing a large longitudinal relaxivity and good biocompatibility represents a significant advance for the targeted imaging and early diagnosis of cancer.