Small Molecule-Drug Conjugates Emerge as a New Promising Approach for Cancer Treatment.

Antibody drug conjugates (ADCs) have emerged as a new promising class of anti- cancer agents. However, limitations such as higher costs and unavoidable immunogenicity due to their relatively large structures cannot be ignored. Therefore, the development of lightweight drugs such as small molecule-drug conjugates (SMDCs) based on the ADC design idea has become a new option for targeted therapy. SMDCs are derived from the coupling of small-molecule targeting ligands with cytotoxic drugs. They are composed of three parts: small-molecule targeting ligands, cytotoxic molecules, and linkers. Compared with ADCs, SMDCs can be more rapidly and evenly dispersed into tumor tissues, with low cost and no immunogenicity. In this article, we will give a comprehensive review of different types of SMDCs currently under clinical trials to provide ideas and inspirations for the development of clinically applicable SMDCs.

Current Strategies for the Treatment of Hepatocellular Carcinoma by Modulating the Tumor Microenvironment via Nano-Delivery Systems: A Review.

Liver cancer remains a global health challenge with a projected incidence of over one million cases by 2025. Hepatocellular carcinoma (HCC) is a common primary liver cancer, accounting for about 90% of all liver cancer cases. The tumor microenvironment (TME) is the internal and external environment for tumor development, which plays an important role in tumorigenesis, immune escape and treatment resistance. Knowing that TME is a unique setting for HCC tumorigenesis, exploration of strategies to modulate TME has attracted increasing attention. Among them, the use of nano-delivery systems to deliver therapeutic agents to regulate TME components has shown great potential. TME-modulating nanoparticles have the advantages of protecting therapeutic agents from degradation, enhancing the ability of targeting HCC and reducing systemic toxicity. In this article, we summarize the TME components associated with HCC, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), endothelial cells and immune cells, discuss their impact on the HCC progression, and highlight recent studies on nano-delivery systems that modulate these components. Finally, we also discuss opportunities and challenges in this field.

Gaussian beam diffraction by two-dimensional refractive index modulation for high diffraction efficiency and large deflection angle.

The propagation of Gaussian beams is analyzed for an acousto-optic deflector by varying the refractive index in two-dimensions with a row of phased array piezoelectric transducers. Inhomogeneous domains of phase grating are produced by operating the transducers at different phase shifts, resulting in two-dimensional index modulation of periodic and sinc function profiles. Also different phase shifts provide a mechanism to steer the grating lobe in various directions and, therefore, the incident angle of the laser beam on the grating plane is automatically modified without moving the beam. Additionally, the acoustic frequency can be varied to achieve the Bragg condition for the new incident angle of the laser beam so that the diffraction efficiency of the deflector is maximized. The Gaussian beam is expressed in terms of planes and the second order coupled mode theory is implemented to analyze the diffraction of the beam. The diffraction efficiency is found to be nearly unity for optimal operating parameters of the acousto-optic device.

Two-dimensional refractive index modulation by phased array transducers in acousto-optic deflectors.

Acousto-optic deflectors are photonic devices that are used for scanning high-power laser beams in advanced microprocessing applications such as marking and direct writing. The operation of conventional deflectors mostly relies on one-dimensional sinusoidal variation of the refractive index in an acousto-optic medium. Sometimes static phased array transducers, such as step configuration or planar configuration transducer architecture, are used to tilt the index modulation planes for achieving higher performance and higher resolution than a single transducer AO device. However, the index can be modulated in two dimensions, and the modulation plane can be tilted arbitrarily by creating dynamic phase gratings in the medium using phased array transducers. This type of dynamic two-dimensional acousto-optic deflector can provide better performance using, for example, a large deflection angle and high diffraction efficiency. This paper utilizes an ultrasonic beam steering approach to study the two-dimensional strain-induced index modulation due to the photoelastic effect. The modulation is numerically simulated, and the effects of various parameters, such as the operating radiofrequency of the transducers, the ultrasonic beam steering angle, and different combinations of pressure on each element of the transducer array, are demonstrated.

Two-dimensional analytic modeling of acoustic diffraction for ultrasonic beam steering by phased array transducers.

Phased array ultrasonic transducers enable modulating the focal position of the acoustic waves, and this capability is utilized in many applications, such as medical imaging and non-destructive testing. This type of transducers also provides a mechanism to generate tilted wavefronts in acousto-optic deflectors to deflect laser beams for high precision advanced laser material processing. In this paper, a theoretical model is presented for the diffraction of ultrasonic waves emitted by several phased array transducers into an acousto-optic medium such as TeO2 crystal. A simple analytic expression is obtained for the distribution of the ultrasonic displacement field in the crystal. The model prediction is found to be in good agreement with the results of a numerical model that is based on a non-paraxial multi-Gaussian beam (NMGB) model.

Dynamic two-dimensional refractive index modulation for high performance acousto-optic deflector.

The performance of an acousto-optic deflector is studied for two-dimensional refractive index that varies as periodic and sinc functions in the transverse and longitudinal directions, respectively, with respect to the direction of light propagation. Phased array piezoelectric transducers can be operated at different phase shifts to produce a two-dimensionally inhomogeneous domain of phase grating in the acousto-optic media. Also this domain can be steered at different angles by selecting the phase shift appropriately. This mechanism of dynamically tilting the refractive index-modulated domain enables adjusting the incident angle of light on the phase grating plane without moving the light source. So the Bragg angle of incidence can be always achieved at any acoustic frequency, and consequently, the deflector can operate under the Bragg diffraction condition at the optimum diffraction efficiency. Analytic solutions are obtained for the Bragg diffraction of plane waves based on the second order coupled mode theory, and the diffraction efficiency is found to be unity for optimal index modulations at certain acoustic parameters.

Site-selective optical coupling of PbSe nanocrystals to Si-based photonic crystal microcavities.

A novel method for patterning optically active colloidal PbSe nanocrystals on Si surfaces is reported. Oleate-capped PbSe nanocrystals were found to adhere preferentially to H-terminated Si surfaces over oxide and alkyl-terminated Si surfaces. Scanning probe lithography was used to oxidize locally a dodecyl monolayer on the Si surface of a silicon-on-insulator wafer prepatterned with photonic crystal microcavities. Aqueous HF was then used to remove the oxide and expose H-terminated Si areas, yielding patterned PbSe nanocrystals on the Si surface after exposure to a nanocrystal solution. This patterning technique allows for the selective deposition of PbSe nanocrystals at the main antinode of the silicon-based microcavities. More than a 10-fold photoluminescence enhancement due to the cavity-nanocrystal coupling was observed.