No abstract

As a very recent technique for time series analysis, Singular Spectrum Analysis (SSA) has been applied in many diverse areas, where an original 1D signal can be decomposed into a sum of components including varying trends, oscillations and noise. Considering pixel based spectral profiles as 1D signals, in this paper, SSA has been applied in Hyperspectral Imaging (HSI) for effective feature extraction. By removing noisy components in extracting the features, the discriminating ability of the features has been much improved. Experiments show that this SSA approach supersedes the Empirical Mode Decomposition (EMD) technique from which our work was originally inspired, where improved results in effective data classification using Support Vector Machine (SVM) are also reported.

The combination of apoptosis and ferroptosis is highly appealing in addressing the tumor heterogeneity‐induced therapy resistance. Reactive oxygen species (ROS)‐based cancer nanomedicine can assemble multiple cell death modalities in a single platform, but the potency of ferroptosis induction is limited. Here, a novel mechano‐responsive polymeric micellar system for selective ferroptosis boosting and ROS therapy sensitization is reported. The mechanophore, ferrocene (Fc) is the key to such design, and the ultrasound can speed up the dissociation of Fc and the release of Fe2+ and hydroxyl radical in the presence of elevated H2O2 in the tumor microenvironment. The Fc‐conjugated amphiphilic copolymers self‐assemble into nanoscale micelles wherein a model sonosensitizer, protoporphyrin IX is physically encapsulated. Upon triggering, the mechano‐responsive micelles produce both singlet oxygen and hydroxyl radical for apoptotic cell death in a model murine breast cancer cell line (4T1). The ROS also depletes intracellular glutathione and thioredoxin, which together with the heightened Fe2+ level boosts lipid peroxidation and hence ferroptotic cell death. The interactive apoptosis and ferroptosis induction and sensitization is further demonstrated in a 4T1 tumor‐bearing mice model with negligible adverse effects. The current work provides a novel approach to simultaneously sensitize apoptosis and ferroptosis for efficient on‐demand cancer therapy.

Traditional singlet oxygen‐based antitumor therapies have been burdened with the necessity of external energy (e.g., light and ultrasound) and harmful dark toxicity. Ascorbate at the pharmacological concentration could accumulate hydrogen peroxide only in the tumor site. It is postulated that the concurrent delivery of ascorbate and nanoparticulate hypochlorous ion (ClO−) could produce singlet oxygen at the tumor site as an energy‐free, tumor‐specific therapy. The ClO− is loaded in a hybrid core–shell nanocarrier consisting of a zeolitic imidazolate framework and amphiphilic poloxamer 188. Intracellular singlet oxygen production is verified in 4T1 cells by the cooperation between hybrid nanocarriers and ascorbate, which induces significant apoptotic cell death. Upon intravenous nanocarriers delivery plus intraperitoneal ascorbate administration to xenograft mice, the in vivo antitumor efficacy of this cooperative nanomedicine is demonstrated without noticeable side‐effects. This work demonstrates a proof‐of‐concept of singlet oxygen‐based chemodynamic therapy for selective tumor eradication, which produces a novel trigger‐free, singlet oxygen‐based cancer therapy without the side effects of traditional photodynamic and sonodynamic therapy.

No abstract

Triggered drug release from anti-tumor nanomedicine is an efficient approach to address the dilemma of systemic nanocarrier stability and on-demand drug liberation in tumor sites.

Vitamin E (α-tocopherol; TPGS) micelle is a robust nanocarrier in delivering hydrophobic active pharmaceutical ingredients, but it is suffering from poor stability that is essential in terms of pharmaceutical and biomedical applications. Taking advantage of the chirality of vitamin E, this work reports the stereoselective stabilization of polymer-vitamin E conjugate micelles. Vitamin E was covalently linked to multivalent methoxy poly(ethylene glycol)-co-poly(glutamic acid), generating amphiphilic conjugates that could self-assemble into micelles. Eight types of micelles were produced via tailored combination of polymer backbone and side chain with different chirality. The particle size and critical micelle concentration analysis demonstrated a correlation between conjugate chirality and micelle stability. The most stable micelles were obtained when poly(glutamic acid) and vitamin E both are dextrorotatory, because of the high degree of α-helix revealed by both circular dichroism spectroscopy and molecular dynamics simulation. This phenomenon was further verified by the fluorescence resonance energy transfer (FRET) analysis in HepG2 cells. The current work not only provides a method to enhance the stability of vitamin E micelles, but also adds an additional facile tool in regulating the stability of polymer conjugate micelles without changing the conjugate composition.

The nonspecific biodistribution of cytotoxic drugs and associated adverse effects greatly limit the efficacy and patient compliance of chemotherapy. To address this, we employed a photoswitchable microtubule inhibitor (Azo-CA4) that was physically loaded in cyclodextrin-bearing micellar nanocarriers through the host-guest interaction. Azo-CA4 was only activated upon ultraviolet (UV) light irradiation to trigger the transition from the "trans" (inactive) to "cis" (active) state. Such conformation change could then induce rapid Azo-CA4 release from micelles without the delay of the onset of therapeutic action. This nanoscale delivery system produced photo-triggered antimitotic and pro-apoptotic effects in MDA-MB-231 cells via a triggered control of microtubule dynamics. The anticancer efficacy of Azo-CA4-loaded micelles was further proved in vivo using a 4T1 tumor-bearing mice model coupled with multiple topical administrations to avoid the penetration problem of UV light. This work provides a new delivery vehicle to aid the application and potential translation of Azo-CA4 as biomedical tools and precision chemotherapeutics.