Application of liposomal technologies for delivery of platinum analogs in oncology

Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™), SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research

Application of liposomal technologies for delivery of platinum analogs in oncology

Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™), SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research

Self-Assembled Core–Shell Nanoparticles for Combined Chemotherapy and Photodynamic Therapy of Resistant Head and Neck Cancers

Combination therapy enhances anticancer efficacy of both drugs <i>via</i> synergistic effects. We report here nanoscale coordination polymer (NCP)-based core–shell nanoparticles carrying high payloads of cisplatin and the photosensitizer pyrolipid, NCP@pyrolipid, for combined chemotherapy and photodynamic therapy (PDT). NCP@pyrolipid releases cisplatin and pyrolipid in a triggered manner to synergistically induce cancer cell apoptosis and necrosis. <i>In vivo</i> pharmacokinetic and biodistribution studies in mice show prolonged blood circulation times, low uptake in normal organs, and high tumor accumulation of cisplatin and pyrolipid. Compared to monotherapy, NCP@pyrolipid shows superior potency and efficacy in tumor regression (83% reduction in tumor volume) at low drug doses in the cisplatin-resistant human head and neck cancer SQ20B xenograft murine model. We elucidated the <i>in vitro</i>/<i>vivo</i> fate of the lipid layer and its implications on the mechanisms of actions. This study suggests multifunctional NCP core–shell nanoparticles as a versatile and effective drug delivery system for potential translation to the clinic

A Chlorin-Based Nanoscale Metal–Organic Framework for Photodynamic Therapy of Colon Cancers

We report here the rational design of the first chlorin-based nanoscale metal–organic framework (NMOF), DBC-UiO, with much improved photophysical properties over the previously reported porphyrin-based NMOF, DBP-UiO. Reduction of the DBP ligands in DBP-UiO to the DBC ligands in DBC-UiO led to a 13 nm red shift and an 11-fold increase in the extinction coefficient of the lowest-energy Q band. While inheriting the crystallinity, stability, porosity, and nanoplate morphology of DBP-UiO, DBC-UiO sensitizes more efficient ¹O₂ generation and exhibits significantly enhanced photodynamic therapy (PDT) efficacy on two colon cancer mouse models as a result of its improved photophysical properties. Both apoptosis and immunogenic cell death contributed to killing of cancer cells in DBC-UiO-induced PDT

Nanoscale Metal–Organic Frameworks for Real-Time Intracellular pH Sensing in Live Cells

Real-time measurement of intracellular pH in live cells is of great importance for understanding physiological/pathological processes and developing intracellular drug delivery systems. We report here the first use of nanoscale metal–organic frameworks (NMOFs) for intracellular pH sensing in live cells. Fluorescein isothiocyanate (FITC) was covalently conjugated to a UiO NMOF to afford F-UiO NMOFs with exceptionally high FITC loadings, efficient fluorescence, and excellent ratiometric pH-sensing properties. Upon rapid and efficient endocytosis, F-UiO remained structurally intact inside endosomes. Live cell imaging studies revealed endo- and exocytosis of F-UiO and endosome acidification in real time. Fluorescently labeled NMOFs thus represent a new class of nanosensors for intracellular pH sensing and provide an excellent tool for studying NMOF–cell interactions

Nanoscale Metal–Organic Frameworks for Real-Time Intracellular pH Sensing in Live Cells

Real-time measurement of intracellular pH in live cells is of great importance for understanding physiological/pathological processes and developing intracellular drug delivery systems. We report here the first use of nanoscale metal–organic frameworks (NMOFs) for intracellular pH sensing in live cells. Fluorescein isothiocyanate (FITC) was covalently conjugated to a UiO NMOF to afford F-UiO NMOFs with exceptionally high FITC loadings, efficient fluorescence, and excellent ratiometric pH-sensing properties. Upon rapid and efficient endocytosis, F-UiO remained structurally intact inside endosomes. Live cell imaging studies revealed endo- and exocytosis of F-UiO and endosome acidification in real time. Fluorescently labeled NMOFs thus represent a new class of nanosensors for intracellular pH sensing and provide an excellent tool for studying NMOF–cell interactions

Calculation model of on-way parameters and heating radius in a superheated steam injection wellbore

As superheated steam is a single-phase gas, it does not fit theories of ordinary steam heat loss calculation models based on two-phase flow. By using the PVT data of superheated steam, this paper builds a calculation model of on-way parameters in the superheated steam injection wellbore. The superheated steam heating area and heating radius formulae are presented. The calculated results for on-the-way change of steams in Well X16 of the Kenneyak oilfield fit well with the field test results. The analysis shows that the temperature of superheated steam varies greatly with heat transfer, the pressure varies greater than for ordinary steam, the steam quality is high when reaching the bottom hole, the steam enthalpy is much higher than for ordinary steam, and the heating radius is wider. 摘要: 过热蒸汽是单相的气体, 以气液两相流理论为基础的普通蒸汽热损失计算模型对其不再适用。通过引入过热蒸汽PVT数据体, 建立了注过热蒸汽井筒沿程参数计算模型。在一定假设的基础上, 理论推导出了过热蒸汽带面积、加热带半径等的数学表达式。利用蒸汽沿程参数计算模型对肯基亚克油田盐上油藏X16井不同状态水蒸汽的沿程变化进行了计算, 结果表明: 计算结果与现场测试结果对应较好。分析认为, 随着热量的传递, 过热蒸汽的温度变化较大, 压力变化也大于普通蒸汽, 到达井底的蒸汽干度特别高, 其热焓值比注普通蒸汽有大幅度提高, 加热半径也有所增加。 Key words: heavy oil, superheated steam, on-way parameter, heating radius, calculation mode

Nanoscale Metal–Organic Framework for Highly Effective Photodynamic Therapy of Resistant Head and Neck Cancer

Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species (e.g., ¹O₂). Here we report the rational design of a Hf–porphyrin nanoscale metal–organic framework, DBP–UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP–UiO efficiently generates ¹O₂ owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile ¹O₂ diffusion through porous DBP–UiO nanoplates. Consequently, DBP–UiO displayed greatly enhanced PDT efficacy both <i>in vitro</i> and <i>in vivo</i>, leading to complete tumor eradication in half of the mice receiving a single DBP–UiO dose and a single light exposure. NMOFs thus represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic

A Calculation Model of the Dimensionless Productivity Index Based on Non-Piston Leading Edge Propulsion Theory in Multiple Oilfield Development Phases

The dimensionless productivity index is an important indicator for measuring the oil production capacity of oilfields. The traditional calculation method of the dimensionless productivity index is not suitable for the continuous multiple development phases of oilfields. In this study, based on Darcy&rsquo;s Law and the theory of non-piston leading edge propulsion, we considered the influence of capillary pressure and derived a differential equation for leading edge propulsion distance. We established a calculation model of the dimensionless productivity index that is suitable for the multiple development phases of oilfields, including water flooding, polymer flooding, and binary compound flooding. The model was applied to the W block of the JZ9-3 oilfield, and the calculation results of the model were compared with the actual statistical results. The results show that the calculation error rates of the dimensionless productivity index in three phases of oilfield development are 4.67%, 17.65%, and 18.50%, respectively, and the average error rate is 10.38% in the overall development phase. The dimensionless productivity index curve shows a trend of first rising, then falling, and finally stabilizing when the pore volume number is included. This calculation model expands the field application scope of the theoretical dimensionless productivity index, which is convenient for application in oilfields, and improves the efficiency of the comprehensive evaluation of oilfields during multiple development phases

Nanoscale Metal–Organic Frameworks for the Co-Delivery of Cisplatin and Pooled siRNAs to Enhance Therapeutic Efficacy in Drug-Resistant Ovarian Cancer Cells

Ovarian cancer is the leading cause of death among women with gynecological malignancies. Acquired resistance to chemotherapy is a major limitation for ovarian cancer treatment. We report here the first use of nanoscale metal–organic frameworks (NMOFs) for the co-delivery of cisplatin and pooled small interfering RNAs (siRNAs) to enhance therapeutic efficacy by silencing multiple drug resistance (MDR) genes and resensitizing resistant ovarian cancer cells to cisplatin treatment. UiO NMOFs with hexagonal-plate morphologies were loaded with a cisplatin prodrug and MDR gene-silencing siRNAs (Bcl-2, P-glycoprotein [P-gp], and survivin) via encapsulation and surface coordination, respectively. NMOFs protect siRNAs from nuclease degradation, enhance siRNA cellular uptake, and promote siRNA escape from endosomes to silence MDR genes in cisplatin-resistant ovarian cancer cells. Co-delivery of cisplatin and siRNAs with NMOFs led to an order of magnitude enhancement in chemotherapeutic efficacy <i>in vitro</i>, as indicated by cell viability assay, DNA laddering, and Annexin V staining. This work shows that NMOFs hold great promise in the co-delivery of multiple therapeutics for effective treatment of drug-resistant cancers