Breast cancer is the most common type of cancer and it is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite chemotherapy’s ample use, it has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target. In this paper, we review recent developments in ultrasound-guided nanocarriers for breast cancer chemotherapy, discuss the relevant challenges, and provide insights into future directions.

A new multiwavelength visible-range-supported opto–ultrasound instrument using a light-emitting diode and ultrasound transducer was developed in order to produce multiwavelength visible light with minimized color aberration errors, and detect ultrasound signals emitted from the target. In the instrument, the developed optical systems can provide multiwavelength optical transmission with low optical aberration within 10-cm ranges that are reasonably flat in the modulation transfer function at spatial frequencies of 20 and 40 lp/mm, except at the end of the diagonal edge of the samples. To assess the instrument capability, we performed pulse–echo responses with Thunnus obesus eye samples. Focused red, green, blue and white light rays from an integrated red, green and blue LED source were produced, and echo signal amplitudes of 33.53, 34.92, 38.74 and 82.54 mV, respectively, were detected from the Thunnus obesus eye samples by a 10-MHz focused ultrasound transducer. The center frequencies of the echo signal when producing red, green, blue and white LED light in the instrument were 9.02, 9.05, 9.21 and 8.81 MHz, respectively. From these tests, we verify that this instrument can combine red, green and blue LED light to cover different wavelengths in the visible-light range and detect reasonable echo amplitudes from the samples.

In optoacoustic (photoacoustic) systems, different echo signal intensities such as amplitudes, center frequencies, and bandwidths need to be compensated by utilizing variable gain or time-gain compensation amplifiers. However, such electronic components can increase system complexities and signal noise levels. In this paper, we introduce a double-Gauss lens to generate a large field of view with uniform light intensity due to the low chromatic aberrations of the lens, thus obtaining uniform echo signal intensities across the field of view of the optoacoustic system. In order to validate the uniformity of the echo signal intensities in the system, an in-house transducer was placed at various positions above a tissue sample and echo signals were measured and compared with each other. The custom designed double-Gauss lens demonstrated negligible light intensity variation (±1.5%) across the illumination field of view (~2 cm diameter). When the transducer was used to measure echo signal from an eye of a bigeye tuna within a range of ±1 cm, the peak-to-peak amplitude, center frequency, and their −6 dB bandwidth variations were less than 2 mV, 1 MHz, and 6%, respectively. The custom designed double-Gauss lens can provide uniform light beam across a wide area while generating insignificant echo signal variations, and thus can lower the burden of the receiving electronics or signal processing in the optoacoustic system.

Conventionally, a bright, very wide-angle optical system is designed as a floating type optical system that moves two or more lens groups composed of multiple lens in order to focus accurately. These have been widely used as phase detection auto focus (AF) methods within conventional digital single-lens reflex (DSLR) cameras. However, a phase detection AF optical system cannot be used when recording motion pictures. In contrast, a compact system camera (CSC) performs AF by the contrast method, where a stepper motor is used as the driving source for moving the optical lens. Nonetheless, to ensure that the focusing lens is lighter, these stepper motors should not have high torque and AF must be possible by moving only one lens. Yet, when focusing is performed with only one lens, aberration change due to focusing lens movement is magnified. Therefore, a very wide-angle optical system comprised of a half-angle of view more than 40 degrees and F of 1/4 has not been developed. Here, a very wide-angle optical system was designed with high resolving power that enables high speed AF, even in contrast mode, by moving only one lens while minimizing aberration change.

The photoacoustic (PA) effect occurs when sound waves are generated by light according to the thermodynamic and optical properties of the materials; they are absorption spectroscopic techniques that can be applied to characterize materials that absorb pulse or continuous wave (CW)-modulated electromagnetic radiation. In addition, the wavelengths and properties of the incident light significantly impact the signal-to-ratio and contrast with photoacoustic signals. In this paper, we reviewed how absorption spectroscopic research results have been used in applying actual photoacoustic effects, focusing on light sources of each wavelength. In addition, the characteristics and compositions of the light sources used for the applications were investigated and organized based on the absorption spectrum of the target materials. Therefore, we expect that this study will help researchers (who desire to study photoacoustic effects) to more efficiently approach the appropriate conditions or environments for selecting the target materials and light sources.

Light emitting diode (LED) and ultrasound have been powerful treatment stimuli for tumor cell growth due to non-radiation effects. This research is the first preliminary study of tumor cell suppression using a macro-lens-supported 460-nm LED combined with high-frequency ultrasound. The cell density, when exposed to the LED combined with ultrasound, was gradually reduced after 30 min of induction for up to three consecutive days when 48-W DC, 20-cycle, and 50 V_p-p sinusoidal pulses were applied to the LEDs through a designed macro lens and to the ultrasound transducer, respectively. Using a developed macro lens, the non-directional light beam emitted from the LED could be localized to a certain spot, likewise with ultrasound, to avoid additional undesirable thermal effects on the small sized tumor cells. In the experimental results, compared to LED-only induction (14.49 ± 2.73%) and ultrasound-only induction (13.27 ± 2.33%), LED combined with ultrasound induction exhibited the lowest cell density (6.25 ± 1.25%). Therefore, our measurement data demonstrated that a macro-lens-supported 460-nm LED combined with an ultrasound transducer could possibly suppress early stage tumor cells effectively.