A Novel Bimodal Imaging Agent Targeting HER2 Molecule of Breast Cancer.

Nanobubble (NB), a newly developed nanoscaled ultrasound contrast agent (UCA) for molecular imaging, has been widely researched for these years. Targeting it with functional molecule, nanobubble can adhere selectively to cellular epitopes and receptors outside the vasculature via enhanced permeability and retention (EPR) effect of tumor blood vessel. To enhance the targeting rate of our previous prepared NBs-Affibody for HER2 (+) breast cancer imaging, we introduced a near-infrared fluorescent (NIRF) dye, IR783, in this study to enhance tumor-specific targeting rate and provide a promising modality for dual-mode imaging. The prepared IR783-NBs-Affibody presented a uniform nanoscale size around 482.7 ± 54.3 nm, good biosecurity, and stability over time. The encapsulation efficiency (EE) of IR-783 was 15.09% in the conjugates leading to a successful NIR fluorescence and ultrasound enhancement imaging ex vivo. IR783-NBs-Affibody was able to automatically accumulate on BT474 cells with a highly increased targeting rate of 85.4% compared with previous NBs-Affibody of 26.6%, while Affibody-guided HER2 binding was only found in HER2-positive cell lines (BT474 and T-47D). The newly developed IR783-NBs-Affibody is characterized with favorable HER2 targeting ability and bimodal imaging capability for breast cancer. Thus, IR783-NBs-Affibody holds great potential in molecular diagnosis for patients with breast cancer.

Pullulan as a stabilizer agent of polymeric nanocapsules for drug delivery

ABSTRACT Polymeric stabilizers have received attention in the preparation of nanostructured systems due to their ability to enhance formulation stability. Considering this, the objective of this work was to prepare poly(ε-caprolactone) nanocapsules using the pullulan as a polymeric stabilizer. The nanocapsules were prepared using the interfacial deposition method of preformed polymers and they were characterized in terms of pH, average diameter, polydispersity index, zeta potential, beclomethasone dipropionate content, encapsulation efficiency, photostability and drug release profiles. The formulations showed physicochemical characteristics consistent with nanocarriers for drug delivery such as: average diameter lower than 270 nm, polydispersity indexes lower than 0.2, negative zeta potential (-22.7 to -26.3 mV) and encapsulation efficiencies close to 100%. In addition, the nanocapsules were able to delay the beclomethasone dipropionate photodegradation under UVC radiation and by the dialysis bag diffusion technique, the nanocapsules were able to prolong the drug release. Thus, pullulan could be considered an interesting excipient to formulate polymeric nanocapsules.

Derivados porfirínicos nanoencapsulados como fotossensibilizadores em terapia fotodinâmica / Nanoencapsulated porphyrin derivatives as photosensitizers in photodynamic therapy

Uma série de oito derivados porfirínicos monocatiônicos, na forma de base-livre e metalados com Zn(II), e tendo grupos metila ou [Ru(bipy)2Cl]+ ligados ao átomo de nitrogênio do substituinte piridil em uma das posições meso do anel, foram sintetizadas e caracterizadas, visando sua aplicação como fotossensibilizadores no tratamento de tumores de pele por TFD. Além de possuírem características anfifílicas que favorecem a sua interação com membranas biológicas, os compostos apresentaram um elevado rendimento quântico de formação de oxigênio singlete, principalmente os derivados metilados das porfirinas base-livre. A baixa solubilidade em meio aquoso, fator limitante da utilização como fotossensibilizadores, foi superada por meio do encapsulamento dos mesmos em micro e nanocápsulas poliméricas, pelo método de coacervação. Duas formulações, uma baseada em hidroxietilcelulose (HEC) e outra na mistura atelocolágeno marinho/goma xantana (ACM), foram preparadas e suas eficiências fotodinâmicas e citotoxicidade frente à células HeLa determinadas. As formulações de ACM mostraram ser não-tóxicas, enquanto os preparados com HEC apresentaram uma pequena, mas significativa citotoxicidade no escuro. Por outro lado, todas as formulações se tornaram tóxicas quando irradiadas com laser de 650 nm ou luz branca proveniente de lâmpada de mercúrio. Dentre as formulações preparadas, as mais ativas foram aquelas preparadas com os derivados porfirínicos base-livre metilados em ACM, provavelmente em virtude da maior eficiência de entrega do composto fotoativo em relação ao sistema polimérico de HEC, aliado aos elevados rendimentos quânticos de formação de oxigênio singlete em relação aos demais compostos. Além disso, o encapsulamento influenciou significativamentente a interação e citolocalização dos fotossensibilizadores, e consequentemente a taxa e o mecanismo de morte celular. Os estudos por microscopia de fluorescência confocal, evidenciaram que as nanocápsulas de ACM são capazes de penetrar na membrana das células, alcançando o citoplasma e liberando gradativamente o composto fotoativo no seu interior. Quando não encapsulada, em solução de dmso, a porfirina se acumula preferencialmente na membrana celular. Consequentemente, neste caso a irradiação levou ao comprometimento da integridade da mesma e o desencadeamento da necrose celular, indesejável na terapia por ocasionar inflamação nos tecidos. Em contrapartida, o tratamento com formulações de fotossensibilizadores nanoencapsulados promoveram menos danos mas favoreceram a apoptose, um mecanismo de morte programada que geralmente leva a regeneração rápida e total dos tecidos, e ausência de processos inflamatórios

A series of eight monocationic porphyrins derivatives as free-base and Zn(II) complexes, with methyl or [Ru(bipy)2Cl]+ groups bond to the nitrogen atom of the meso-pyridyl substituent, were synthesized and characterized aiming their application as photosensitizers in the treatment of skin tumors by Photodynamic Therapy (PDT). Those compounds, especially the methylated derivatives of the free-base porphyrins, are potentially useful because showed higher quantum yields for the photoinduced formation of singlet oxygen and amphiphilic character, that enhanced their interaction with biological membranes. The low solubility in aqueous media, a limiting factor for use as photosensitizers, was overcome by encapsulating them in polymeric micro-and nanocapsules using the coacervation method. Two formulations, one based on hydroxyethyl cellulose (HEC) and another in the marine atelocollagen/xanthan gum (MAC) mixture were prepared and their photodynamic efficiencies and cytotoxicity against HeLa cells determined. The MAC formulations were shown to be non-toxic, while the HEC presented a small but significant cytotoxicity in the dark. On the other hand, all formulations become toxic when irradiated with 650 nm laser or white light from a mercury lamp source. The most actives, among all formulations, were those prepared using the methylated free-base porphyrin derivatives and MAC, probably due to the higher delivery efficiency of the photosensitizers in relation to the formulations prepared with HEC, associated with their higher quantum yields of photoinduced formation of singlet oxygen of those species as compared with the other compounds. In addition, the encapsulation influenced the interaction and cytolocalization of the photosensitizers, and consequently the rate and mechanism of cell death. The MAC nanocapsules were shown to penetrate the cell membrane by confocal fluorescence microscopy, reaching the cytoplasm where gradually released the photoactive compound. However, the porphyrin derivatives preferentially accumulated in the cell membrane when in DMSO solution. Consequently, the irradiation compromised the membrane integrity leading to necrosis, an undesirable process since cause tissue inflammation. In contrast, the treatment with encapsulated photosensitizer formulations promoted a much lower level of photoinduced damage and apoptosis, a more desirable death mechanism characterized by a complete and rapid regeneration of tissues and absence of inflammatory processes

Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects.

The in vitro labeling of stem or therapeutic cells with engineered nanoparticles with the aim of transplanting these cells into live animals and, for example, noninvasively monitoring their migration, is a hot topic in nanomedicine research. It is of crucial importance that cell-nanoparticle interactions are studied in depth in order to exclude any negative effects of the cell labeling procedure. To date, many disparate results can be found in the literature regarding nanoparticle toxicity due to the great versatility of different parameters investigated. In the present work, an overview is presented of different types of nanomaterials, focusing mostly on iron oxide nanoparticles, developed for biomedical research. The difficulties in assessing nanoparticle-mediated toxicity are discussed, an overview of some of the problems encountered using commercial (dextran-coated) iron oxide nanoparticles is presented, several key parameters are highlighted and novel methods suggested--emphasizing the importance of intracellular nanoparticle degradation and linking toxicity data to functional (i.e., cell-associated) nanoparticle levels, which could help to advance any progress in this highly important research topic.