The existing of avidity cancer stem cells (CSCs) made it an optical strategy to kill cancer cells and CSCs at the same time. Here, we constructed a CSCs specific nanocarrier naming T-S-NLC using the CD133+ targeting peptide TISWPPR (TR) as the targeting moiety attached to the distal end of PEG on salinomycin (Sal) loaded nanostructured lipid carriers (NLC), its pharmaceutical characteristics proved it 128.73 ± 2.09 nm, anionic spheroid with sustained release profile. It's in vitro targeting effect in CD133+ CSCs indicated that it exhibited superior CSCs internalization over non-modified NLC or free drug. Afterwards, it was used in combination with previously designed EGFR specific A-P-NLC (AEYLR peptide-PEG-modified paclitaxel loaded NLC) to achieve the goal to kill the cancer cells and CSCs, simultaneously. The in vitro tumor targeting effect of T-S-NLC + A-P-NLC was affirmed by cellular uptake and proliferation inhibition effect in NCI-H1299 and S180 cell lines showing advanced results over single preparation groups. In vivo tumor targeting effect in S180 tumor-bearing mice also validated the better tumor accumulative effect of the combined group. Last but not least, the in vivo antitumor effect strongly identified the greater tumor suppression effect of T-S-NLC + A-P-NLC than single preparation groups or combined use of free drugs while maintaining a good living state of the mice. To sum up, the combined usage of PTX and Sal active targeting NLC naming A-P-NLC + T-S-NLC which killed cancer cells and CSCs at the same time was a promising drug delivery system.

Mesoporous carriers have been extensively applied to improve the dissolution velocity and bioavailability of insoluble drugs. The goal of this work was to compare the drug-loading efficiency (LE) and drug-dissolution properties of mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) as drug vectors oral delivery of water-insoluble drugs. For this purpose, MSN and MCN with similar particle size, surface area, and mesoporous diameter were prepared to precisely evaluate the effects of different textures on the drug-loading and dissolution behavior of insoluble drugs. Carvedilol (CAR), a Bio-pharmaceutic Classification System (BCS) class II drug, was loaded in the MSN and MCN by the solvent adsorption method and solvent evaporation method with different carrier–drug ratios. The carboxylated MCN (MCN–COOH) had a higher LE for CAR than MSN for both the two loading methods due to the strong adsorption effect and π–π stacking force with CAR. In vitro drug dissolution study showed that both MSN and MCN-COOH could improve the dissolution rate of CAR compared with the micronized CAR. In comparison to MSN, MCN-COOH displayed a slightly slower dissolution profile, which may be ascribed to the strong interaction between MCN-COOH and CAR. Observation of cell cytotoxicity and gastrointestinal mucosa irritation demonstrated the good biocompatibility of both MSN and MCN–COOH. The present study encourages further research of different carriers to determine their potential application in oral administration.

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

To strengthen the anti-tumour efficacy and weaken the side effects, a nano targeted drug delivery system was constructed. The nanostructured lipid carriers (NLCs) were prepared by the melt-emulsification method. Modified with the octaarginine, thiolytic cleavable polyethylene glycol (PEG) and targeting peptide simultaneously on the surface, this multifunctional NLC could not only actively target to tumour tissues, but also control the cell penetration effect of the octaarginine easily by a safe reducing agent l-cysteine (l-Cys). In the present study, the pharmaceutical characteristics, the cytotoxicity and cellular uptake on NCI-H1299 cells in vitro, the biodistribution and targeting effect and anti-tumour ability in vivo were employed to evaluate the formulations. As the results revealed, various NLCs had a mean particle size of about 40 nm and a positive zeta potential of about 10 mV. The optimum density of cleavable PEG was confirmed as 10% and the best concentration of l-cysteine was determined as 20 mM via the qualitative and quantitative cellular uptake study. Based on these outcomes, the multiply decorated NLC manifested a great cell growth inhibition with the increased concentration of paclitaxel (PTX). Moreover, it preferred to accumulate at tumours, but not normal organs in vivo. Compared with Taxol^®, this preparation demonstrated stronger anti-tumour efficacy and better security. Therefore, the multifunctional NLC can be considered as a promising drug delivery system targeting to tumours.

We constructed a dual ligands-modified nanostructured lipid carrier (NLC) called PAR-NLC, in which the epidermal growth factor receptor (EGFR)-targeted small peptide AEYLR was attached to the distal end of PEG(2000) anchored on the NLC surface naming PEG-AEYLR, and poly-arginine (R8) as a classic cell-penetrating peptide was attached directly to the NLC surface. PAR-NLC was near-spherical particle with average size similar to 50nm and zeta potential at +14.09mV; the cellular uptake of PAR-NLC showed synergistic effect of the two peptides, presented as significant superior cellular uptake in EGFR-positive cells NCI-H1299 and S180 over EGFR-negative cell K562. In the animal optical imaging study, 2 h after the administration of the Dir-loaded PAR-NLC, maximum Dir signal appeared in tumor tissue, indicating prompt tumor targeting effect, as time prolonged to 48 h, the Dir signal attenuated in the organs except tumor, suggesting constant clearance from the body. In the in vivo antitumor study, in premise of the same dose, paclitaxel-loaded PAR-NLC exhibited better antitumor and safety effect than Taxol, the body weight of the mice was more stable and tumor size was smaller. In summary, PAR-NLC was a potential drug carrier to deliver anticancer drugs safely and effectively.