High Drug-Loading Nanomedicines for Tumor Chemo-Photo Combination Therapy: Advances and Perspectives.

The combination of phototherapy and chemotherapy (chemo−photo combination therapy) is an excellent attempt for tumor treatment. The key requirement of this technology is the high drug-loading nanomedicines, which can load either chemotherapy drugs or phototherapy agents at the same nanomedicines and simultaneously deliver them to tumors, and play a multimode therapeutic role for tumor treatment. These nanomedicines have high drug-loading efficiency (>30%) and good tumor combination therapeutic effect with important clinical application potential. Although there are many reports of high drug-loading nanomedicines for tumor therapy at present, systematic analyses on those nanomedicines remain lacking and a comprehensive review is urgently needed. In this review, we systematically analyze the current status of developed high drug-loading nanomedicines for tumor chemo−photo combination therapy and summarize their types, methods, drug-loading properties, in vitro and in vivo applications. The shortcomings of the existing high drug-loading nanomedicines for tumor chemo−photo combination therapy and the possible prospective development direction are also discussed. We hope to attract more attention for researchers in different academic fields, provide new insights into the research of tumor therapy and drug delivery system and develop these nanomedicines as the useful tool for tumor chemo−photo combination therapy in the future.

Nano-Carriers of Combination Tumor Physical Stimuli-Responsive Therapies.

With the development of nanotechnology, Tumor Physical Stimuli-Responsive Therapies (TPSRTs) have reached a new stage because of the remarkable characteristics of nanocarriers. The nanocarriers enable such therapies to overcome the drawbacks of traditional therapies, such as radiotherapy or chemotherapy. To further explore the possibility of the nanocarrier-assisted TPSRTs, scientists have combined different TPSRTs via; the platform of nanocarriers into combination TPSRTs, which include Photothermal Therapy (PTT) with Magnetic Hyperthermia Therapy (MHT), PTT with Sonodynamic Therapy (SDT), MHT with Photodynamic Therapy (PDT), and PDT with PTT. To achieve such therapies, it requires to fully utilize the versatile functions of a specific nanocarrier, which depend on a pellucid understanding of the traits of those nanocarriers. This review covers the principles of different TPSRTs and their combinations, summarizes various types of combination TPSRTs nanocarriers and their therapeutic effects on tumors, and discusses the current disadvantages and future developments of these nanocarriers in the application of combination TPSRTs.

Ultrathin surface coated water-soluble cobalt ferrite nanoparticles with high magnetic heating efficiency and rapid in vivo clearance.

To obtain magnetic nanoparticles with high magnetic heating efficiency and rapid in vivo clearance, this study utilized an improved linear response theory model to theoretically simulate the specific absorption rate (SAR) value versus the particle size of cobalt ferrite nanoparticles (CFNPs). An accurate SAR curve consistent with experimental results was obtained using cubes instead of spheres as the shape of CFNPs, given that cube was closer to the actual shape of prepared CFNPs. Under the guidance of simulation, we predicted and prepared water-soluble cubic CFNPs of 10-13 nm in size, with an ultrathin surface coating less than 1 nm in thickness. These CFNPs were experimentally verified to have high magnetic heating efficiency and rapid in vivo clearance rate. Our CFNPs of 11.8 nm in size had a high intrinsic loss power of 12.11 nHm2/kg. Most of the cells were killed within 30 min under magnetic heating with CFNPs. In an in vivo study, these CFNPs can heat a tumor area to 45 °C (ΔT > 9 °C) within 120 s under a weak alternating magnetic field (27 kA/m, 115 kHz). Notably, these CFNPs had significant tumor inhibition rate in vivo and can be cleared from the body by more than 64% within 2 weeks, demonstrating excellent rapid in vivo clearance. This result was close to the clearance level of the magnetic resonance imaging contrast agent Feridex. Therefore, our CFNPs had high magnetic heating efficiency and rapid in vivo clearance rate, indicating their great potential for future clinical applications.

Thermochromism-induced temperature self-regulation and alternating photothermal nanohelix clusters for synergistic tumor chemo/photothermal therapy.

To improve the inherent defects of chemotherapy and photothermal therapy (PTT), we design a novel thermochromism-induced temperature self-regulation and alternating photothermal system based on iodine (I2)-loaded acetylated amylose nanohelix clusters (ILAA NHCs) under the guidance of molecular dynamic simulation in which I2 is loaded into the helical cavity of acetylated amylose (AA) by hydrophobic interaction. ILAA NHCs perform versatile photothermal conversion through their unique reversible thermochromism. Upon irradiation, I2 is gradually released and the ILAA NHCs turn into colorless. The laser is then penetrated deeply into the tissue for deep-seated heating, and the ILAA NHCs' color can be recovered by reversible thermochromism because of I2 reloading into the ILAA NHCs. When the process is repeated, the temperature can be controlled in a certain range. This alternating light-to-heat conversion significantly improve the effect of PTT. Meanwhile, I2 efficiently acts dual functions of chemotherapy and PTT. Results show that the photothermal depth by ILAA NHCs is 2.1-fold than other common photothermal agents (PTAs), and the irradiated region exhibits a lower surface temperature. In vitro and in vivo experiments both provide ILAA NHCs an excellent comprehensive antitumor effect with synergistic chemo/PTT, indicating versatile potential for tumor chemo/PTT.

Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo.

A safe and effective vaccine adjuvant is important in modern vaccines. Various Chinese herbal polysaccharides can activate the immune system. Cistanche deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo. In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments. In addition, its immunomodulatory activity was also observed in mice. WPCD effectively improved the titers of IgG, IgG1 and IgG2a and markedly enhanced the proliferation of T and B cells, the production of IFN-γ and IL-4 in CD4+ T cells and the expression level of IFN-γ in CD8+ T cells better than Alum. Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and CD80 on DCs in spleen and down-regulate the Treg frequency. The study suggests that polysaccharides of Cistanche deserticola are a safe and effective vaccine adjuvant for eliciting both humoral immunity and cellular immunity by activating DCs via TLR4 signaling pathway.

Temperature field simulation and phantom validation of a Two-armed Spiral Antenna for microwave thermotherapy.

In this paper, an Archimedean planar spiral antenna for the application of thermotherapy was designed. This type of antenna was chosen for its compact structure, flexible application and wide heating area. The temperature field generated by the use of this Two-armed Spiral Antenna in a muscle-equivalent phantom was simulated and subsequently validated by experimentation. First, the specific absorption rate (SAR) of the field was calculated using the Finite Element Method (FEM) by Ansoft's High Frequency Structure Simulation (HFSS). Then, the temperature elevation in the phantom was simulated by an explicit finite difference approximation of the bioheat equation (BHE). The temperature distribution was then validated by a phantom heating experiment. The results showed that this antenna had a good heating ability and a wide heating area. A comparison between the calculation and the measurement showed a fair agreement in the temperature elevation. The validated model could be applied for the analysis of electromagnetic-temperature distribution in phantoms during the process of antenna design or thermotherapy experimentation.

[The determination of konjac glucomannan in konjac refined powder and monosaccharide compositions by HPLC].

OBJECTIVE: To establish a quantitative method for the content determination and monosaccharide composition analysis of Konjac glucomannan (KGM) in Konjac refined powder by pre-column derivatization high performance liquid chromatographic method (HPLC). METHOD: The two derivatives combined reducing monosaccharides with 1-phenyl-3-methyl-5-pyrazolone (PMP) were separated by reverse-phase HPLC using a developed fragment gradient elution process, and monitored by ultraviolet detector at 250 nm. The broad reagent peak of PMP was separated very well from all the PMP-sugars, and good separation was achieved for derivatives of mannose and glucose. The quantitative methods of two reducing monosaccharides were studied by the method combined internal and external standard; while the KGM content in Konjac refined powder was determined. RESULT: Linearity of glucose was good (r = 0.9990) in range of 1.002-8.016 nmol; while mannose (r = 0.9994) in range of 1.001-8.008 nmol. The average recovery of this method was 98.1%, RSD of repeatability was 1.72%. KGM content in Konjac refined powder was 79.5%, ratio of glucose to mannose in KGM was 1:1.51. CONCLUSION: This method is a sample, convenient and rapid method that can determine KGM content and analyze monosaccharide compositions in KGM, which will be helpful to quality assessment of Konjac refined powder.

[Studies on ultrasonic wave extracting method determining konjac glucomannanin konjac refined powder].

OBJECTIVE: To investigate the effect of ultrasonic wave on extracting Konjac Glucomannan(KGM) in Konjac refined powder. METHOD: Free reduced sugar in Konjac refined powder was removed and Konjac refined powder in the aqueous solution was processed by ultrasonic wave and KGM content was measured by spectrophotometry. RESULT: KGM content in the Konjac refined powder aqueous solution by ultrasonic process at fixed 40 kHz, 100 W, 30-45 min was equal to that by routine method at 4 h; whereas, by 1 h of ultrasonic process, KGM content was significantly enhanced than that by 4 h of routine method(P < 0.01), enhancement rate was 6.5%. Linearity of standard glucose was good (r = 0.9996) in range of 0.2-1.6 mg. The average recovery was 97.8%, RSD of repeatability was 1.27%. CONCLUSION: Ultrasonic extraction in aqueous solution is a reliable and rapid method that can enhance extraction efficiency of KGM in Konjac refined powder.