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Molecular targeted therapy significantly improved the therapeutic efficacy in non-small cell lung cancer (NSCLC) patients with driver gene mutations but also with new toxicity profiles. Although most patients treated with these drugs developed relatively controllable toxicity, significant pulmonary toxicity events, including interstitial lung disease, occurred in a small proportion of patients and can lead to discontinuation or even be life-threatening. Pulmonary toxicity associated with these anti-tumor drugs is a problem that cannot be ignored in clinical practice. The prompt diagnosis of drug-related lung injury and the consequent differential diagnosis with other forms of pulmonary disease are critical in the management of pulmonary toxicity. Current knowledge of the pathophysiology and management of pulmonary toxicity associated with these targeted drugs is limited, and participants should be able to identify and respond to the development of drug-induced pulmonary toxicity. This review offers information about the potential pathogenesis, risk factors and management for the development of these events based on the available literature. This review focused on pulmonary toxicities in driver gene-positive NSCLC therapy by describing the related adverse events to promote the awareness and management of this important toxicity related to antitumor-targeted therapy. [ABSTRACT FROM AUTHOR]

In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and −15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis. [ABSTRACT FROM AUTHOR]

In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and −15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Alendronate-monoethyl adipate-(hydrazone)-doxorubicin conjugate ( ALN- MA-hyd- DOX) was synthesized to specifically deliver doxorubicin ( DOX) to bone tumor tissue. The binding kinetics of ALN- MA-hyd- DOX with hydroxyapatite ( HA) and natural bone were detected by using spectrophotometer. Cytotoxicity of ALN- MA-hyd- DOX on tumor cells was determined by MTT [3-(4,5-dimethylthiaol-2-yl)-2,5-diphenyl-tetrazolium bromide] method. The cellular uptake of ALN- MA-hyd- DOX was observed by using fluorescence microscopy. The in vivo antitumor activity of ALN- MA-hyd- DOX was investigated by using tumor-bearing nude mice model. The results indicated that ALN- MA-hyd- DOX was able to quickly bind with HA and natural bone. ALN- MA-hyd- DOX immobilized on the natural bone released more DOX in p H 5.0 medium than that in p H 6.0 or 7.4 medium. The cytotoxicity of ALN- MA-hyd- DOX toward A549 cells and MDA- MB-231/ ADR cells was greater than DOX. ALN- MA-hyd- DOX was rapidly uptaken by A549 cells and MDA- MB-231/ ADR cells. Compared with the same dose of free DOX, ALN- MA-hyd- DOX significantly decreased tumor volume of tumor-bearing nude mice. DOX mainly distributed in bone tumor tissue after ALN- MA-hyd- DOX was intravenously administered to tumor-bearing nude mice, whereas DOX distributed through the whole body after DOX was intravenously administered to tumor-bearing nude mice. These findings implied that the ALN- MA-hyd- DOX was a promising bone-targeted conjugate for treating bone neoplasms. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2293-2303, 2015 [ABSTRACT FROM AUTHOR]

In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor. [ABSTRACT FROM AUTHOR]