In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers.

Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis.

Biodegradable poly(lactic acid) (PLA) presents suitable physicochemical properties and biocompatibility for biomedical engineering. However, PLA has some drawbacks, such as low cell adhesion, biological inertness, low degradation rate, and acid degradation by-products. In this review, recent progress on strategies to address these problems is summarized, including novel fabrication techniques, high-performance PLA composites, and their applications for tissue engineering and drug delivery. The scaffolds, especially for bone regeneration, blood vessels, organs, and skin regeneration are evaluated, in terms of in vivo and in vitro biocompatibility and biodegradability. The enhanced mechanical, thermal, and rheological properties of PLA biocomposites are analyzed in detail. PLA biocomposites for drug encapsulation, sustained release, and tumor-targeting are also reviewed. Furthermore, the challenges and future perspectives on PLA-based biocomposites are discussed.

Current applications of poly(lactic acid) composites in tissue engineering and drug delivery

Traditional treatment approaches for cancer involve intravenous chemotherapy or other forms of drug delivery. These therapeutic measures suffer from several limitations such as nonspecific targeting, poor biodistribution, and buildup of drug resistances. However, significant technological advancements have been made in terms of superior modes of drug delivery over the last few decades. Technical capability in analyzing the molecular mechanisms of tumor biology, nanotechnology─particularly the development of biocompatible nanoparticles, surface modification techniques, microelectronics, and material sciences─has increased. As a result, a significant number of nanostructured carriers that can deliver drugs to specific cancerous sites with high efficiency have been developed. This particular maneuver that enables the introduction of a therapeutic nanostructured substance in the body by controlling the rate, time, and place is defined as the nanostructured drug delivery system (NDDS). Because of their versatility and ability to incorporate features such as specific targeting, water solubility, stability, biocompatibility, degradability, and ability to reverse drug resistance, they have attracted the interest of the scientific community, in general, and nanotechnologists as well as biomedical scientists. To keep pace with the rapid advancement of nanotechnology, specific technical aspects of the recent NDDSs and their prospects need to be reported coherently. To address these ongoing issues, this review article provides an overview of different NDDSs such as lipids, polymers, and inorganic nanoparticles. In addition, this review also reports the challenges of current NDDSs and points out the prospective research directions of these nanocarriers. From our focused review, we conclude that still now the most advanced and potent field of application for NDDSs is lipid-based, while other significantly potential fields include polymer-based and inorganic NDDSs. However, despite the promises, challenges remain in practical implementations of such NDDSs in terms of dosage and stability, and caution should be exercised regarding biocompatibility of materials. Considering these aspects objectively, this review on NDDSs will be particularly of interest for small-to-large scale industrial researchers and academicians with expertise in drug delivery, cancer research, and nanotechnology.

Recent Progress in Nanostructured Smart Drug Delivery Systems for Cancer Therapy: A Review.

Nanoparticle-based drug delivery systems for controllable photodynamic cancer therapy

Nanotechnology in ovarian cancer: Diagnosis and treatment.

Ovarian cancer is the most leading cause of death and the third most common gynecologic malignancy in women. Traditional chemotherapy has inevitable drawbacks of nonspecific tumor targeting, high toxicity, and poor therapeutic efficiency. In order to overcome such shortcomings, we prepared a novel nano-carrier drug-delivery system to enhance the anti-tumor efficiency. In vitro characterizations of nano-carriers were determined by TEM, DLS. Cell viability was measured by MTT method. RT-PCR was performed to measure the expression of FARα in three ovarian cancer cell lines. The drug-release study and the uptaken study were measured in vitro. The pharmacokinetic and the drug distribution study were verified by HPLC methods in vivo. The enhanced anti-tumor efficiency of FA-NP was evaluated by the tumor inhibitory rate in vivo. Paclitaxel (PTX)-loaded nanoparticles (NPs) (PTX-PEG-PLA-NP and PTX-PEG-PLA-FA-NP) were prepared successfully, and the drug-release study showed that the cumulative release rates of NP groups were much less than free PTX group. The pharmacokinetic study showed that the elimination phase of two kinds of NP groups were much longer than that of PTX group. The drug distribution in different tissues showed that the peak-reach time was 2 h in the PTX group and 6 h in both NP groups. All of these results confirmed the excellent slow-release effects of both kinds of nano-carriers. More importantly, we confirmed that PTX-PEG-PLA-FA-NP had greater uptake by SK-OV-3 cells than PTX-PEG-PLA-NP and free PTX in vitro. A drug-distribution study of tumor-bearing mice demonstrated that the PTX concentration of tumor tissues in the PTX-PEG-PLA-FA-NP group was 3 times higher than the other two groups. PTX-PEG-PLA-FA-NP was uptaken much more by SK-OV-3 cells than PTX-PEG-PLA-NP and free PTX. Eventually, based on the slow-release effect and tumor-targeting characteristics of PTX-PEG-PLA-FA-NP, a cytotoxicity test indicated that PTX-PEG-PLA-FA-NP was much more toxic to SK-OV-3 cells than the controls. The tumor inhibitory rate in the PTX-PEG-PLA-FA-NP group of tumor-bearing mice was about 1.5 times higher than the controls. The tumor targeting and anti-tumor efficiency of PTX-PEG-PLA-FA-NP were confirmed both in vitro and in vivo. We developed an ovarian cancer targeting nano-carrier drug delivery system successfully, which showed perfect ovarian cancer targeting and anti-tumor effect, thus have the potential to be a new therapy strategy for ovarian cancer patients.

/pdf/development-and-evaluation-of-novel-tumor-targeting-56ed3pu4er.pdf

Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo

Development of novel ST68/PLA-PEG stabilized ultrasound nanobubbles for potential tumor imaging and theranostic.

Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, P<0.05), there was no significant difference in the survival time of animals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer.

/pdf/enhanced-effect-of-photodynamic-therapy-in-ovarian-cancer-4t1hvrd2aa.pdf

Enhanced effect of photodynamic therapy in ovarian cancer using a nanoparticle drug delivery system

The invention discloses a preparation method of a hypocrellin B nanoparticle. The preparation method includes: (1), dissolving a carrier polymer in an organic solution to obtain a solution A with the concentration of 10-20mg/ml; (2), dissolving hypocrellin B in an organic solution to obtain a solution B with the concentration of 1-2mg/ml; (3), evenly mixing the solution A with the solution B according to a volume ratio of (1-14):1 to obtain a drug polymer organic solution with the uniform concentration; (4), dripping the drug polymer organic solution prepared in the step (3) in water while stirring, and performing standing for 12-24 hours to obtain a micellar solution, wherein the volume ratio of the drug polymer organic solution to the water is 1:(10-30); (5), transferring the micellar solution into a dialysis bag, putting the dialysis bag in water for dialysis, and dialyzing the organic solution to obtain the hypocrellin B nanoparticle. The hypocrellin B nanoparticle prepared according to the method is spherical and regular morphologically, high in dispersity, uniform and not sticky when being observed by a transmission electron microscope.

Hypocrellin B nanoparticle and preparation method thereof

The invention discloses a preparation method of doxorubicin hydrochloride magnetic nanoparticles. The preparation method comprises the following steps: (1) dissolving nano block polymer polyethylene glycol-polylactic acid in dimethyl formamide to prepare a solution A; (2) dissolving doxorubicin hydrochloride in dimethyl formamide to prepare a solution B; (3) adding triethylamine into the solution B, and performing the deionization ultrasonic dissolving on the doxorubicin hydrochloride; (4) dissolving ferroferric oxide powder in tetrahydrofuran, and ultrasonically dispersing to obtain a solution C; (5) dropwise adding the deionized solution B into the solution A under a stirring condition; (6) stirring and uniformly mixing the doxorubicin hydrochloride and nano blocks, and volatilizing organic solvent to obtain medicine carrying micelle; (7) dropwise adding the solution C into the medicine carrying nano micelle obtained in the step (6), and uniformly stirring; (8) dialyzing to obtain magnetic medicine carrying nano micelle; and (9) adding a freeze drying protective agent into the nano micelle to obtain the magnetic medicine carrying nanoparticles. The method is simple in operation procedures and easy in operation.

Doxorubicin hydrochloride magnetic nanoparticles and preparation method thereof

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