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Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA–chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)–chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA–IR-780–NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark. [ABSTRACT FROM AUTHOR]

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers. [ABSTRACT FROM AUTHOR]

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent. [ABSTRACT FROM AUTHOR]

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers.

Background/Objectives: Focused ultrasound (FUS) and microbubble (MB) exposure is a promising technique for targeted drug delivery to the brain; however, refinement of protocols suitable for large-volume treatments in a clinical setting remains underexplored. Methods: Here, the impacts of various sonication parameters on blood-brain barrier (BBB) permeability enhancement and tissue damage were explored in rabbits using a clinical-prototype hemispherical phased array developed in-house, with real-time 3D MB cavitation imaging for exposure calibration. Initial experiments revealed that continuous manual agitation of MBs during infusion resulted in greater gadolinium (Gd) extravasation compared to gravity drip infusion. Subsequent experiments used low-dose MB infusion with continuous agitation and a low burst repetition frequency (0.2 Hz) to mimic conditions amenable to long-duration clinical treatments. Results: Key sonication parameters-target level (proportional to peak negative pressure), number of bursts, and burst length-significantly affected BBB permeability enhancement, with all parameters displaying a positive relationship with relative Gd contrast enhancement ( p < 0.01). Even at high levels of BBB permeability enhancement, tissue damage was minimal, with low occurrences of hypointensities on T2*-weighted MRI. When accounting for relative Gd contrast enhancement, burst length had a significant impact on red blood cell extravasation detected in histological sections, with 1 ms bursts producing significantly greater levels compared to 10 ms bursts ( p = 0.03), potentially due to the higher pressure levels required to generate equal levels of BBB permeability enhancement. Additionally, albumin and IgG extravasation correlated strongly with relative Gd contrast enhancement across sonication parameters, suggesting that protein extravasation can be predicted from non-invasive imaging. Conclusions: These findings contribute to the development of safer and more effective clinical protocols for FUS + MB exposure, potentially improving the efficacy of the approach.

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome. [ABSTRACT FROM AUTHOR]

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome.

Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA-chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)-chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA-IR-780-NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark.

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis . In vivo experiments showed that after i.v. administration, mPLGA/IR775-ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm 3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.